Objective: To analyze the prevalence of and risk factors for infections in patients with pemphigus, and to evaluate their effect on prognosis. Methods: Clinical data were collected from 182 inpatients with pemphigus in Department of Dermatology, Xijing Hospital, Fourth Military Medical University from May 2011 to May 2017, and retrospectively analyzed. Associations of infection rates with age, disease severity, comorbidities, maximum dose of glucocorticoids, hospitalization duration and costs were analyzed. Statistical analysis was carried out with SPSS 22.0 software by using Logistic regression analysis for analyzing risk factors for concurrent infections in pemphigus patients who were hospitalized for the first time. Results: Among the 182 patients, 82 (45.05%) experienced infections. Additionally, 107 pathogenic strains were cultured from secretions from skin lesions of 77 patients, including 60 strains of Staphylococcus aureus (56.07%) , and 58 Staphylococcus aureus strains were resistant to penicillin (96.67%) . Among the 182 patients, infections were observed in 11 of 14 patients with hypoproteinemia, 69 (41.07%) of 168 patients without hypoproteinemia, 4 (4.81%) of 27 patients with mild pemphigus, 34 (37.7%) of 90 patients with moderate pemphigus and 44 (67.69%) of 65 patients with severe pemphigus. Logistic regression analysis showed that the prevalence rate of infections was significantly higher in the patients with hypoproteinemia than in those without hypoproteinemia (OR = 5.559, 95% CI 1.053-29.347, P = 0.043) . Compared with the patients with mild pemphigus, the prevalence rate of infections significantly increased in the patients with moderate (OR = 4.676, 95% CI 1.276-17.123, P < 0.05) or severe pemphigus (OR = 16.529, 95% CI 4.183-65.314, P < 0.001) . The prevalence of infections in patients with pemphigus was unaffected by gender, types of pemphigus, or the presence of hypertension or diabetes (all P > 0.05) . Among the 145 patients who were followed up, 33 were completely cured, 67 were cured clinically, 23 received improvement, 10 experienced relapse or exacerbation, and 12 died. Of the 12 dead patients, 3 died of pneumonia, 2 died of exacerbated pemphigus and skin infections, and 1 died of sepsis. Conclusions High disease severity and hypoproteinemia are risk factors for infections in patients with pemphigus. Bacterial infection is a common complication in patients with pemphigus, and severe infections are one of the causes of death in patients with pemphigus.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT). Methods: Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL-NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed. Results: Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage Ⅳ E. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA-1, granzyme B, but did not express CD20, CD79a, and CD5. Ki-67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow-up with a survival period of only 1 week to 13 months. Conclusions Pulmonary ENKTL-NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.

Objective To demonstrate the clinical characteristics and prognosis of invasive pulmonary aspergillosis (IPA) in respiratory intensive care unit (ICU), for early diagnosis and treatment. Methods The clinical features, treatment and outcome of 17 patients diagnosed as IPA in RICU from May 2015 to April 2018 were analyzed retrospectively. Results The basic diseases of 17 patients were mostly chronic respiratory diseases (14 cases, while 11 cases were chronic obstructive pulmonary disease). One case was proven by IPA criteria, 13 cases were probable and 3 cases were possible. All patients were treated with broad-spectrum antibiotics during hospitalization, and 6 patients were treated with glucocorticoids (oral/intravenous) within 3 weeks of admission and during hospitalization. The main clinical symptoms included cough sputum, dyspnea and fever, among which 4 cases had hemoptysis. Infiltrates were seen in 8 cases, multiple nodules with cavitary lesions in 4 cases, multiple small nodules along the bronchi in 2 cases, and left upper lobe consolidation in the proven case. Sixteen patients were treated with voriconazole alone or in combination with caspofungin. Fourteen patients were tested for voriconazole serum concentration, while 4 were in normal range, 10 were elevated (2 cases were significantly elevated, ＞10 μg/L). Serum concentration of bilirubin did not increase significantly in all paitents after treatment. Serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 4 cases with elevated serum concentration of voriconazole and 2 cases with normal serum concentration of voriconazole. Patients with elevated voriconazole concentration did not show significant difference in prognosis compared with those with normal concentration. Eight cases were improved and discharged and 9 gave up and died due to the worsening of the disease. Eight patients received mechanical ventilation (6 cases were invasive and 2 cases were non-invasive), 7 of them eventually gave up treatment and died. Conclusions The clinical features of chronic respiratory diseases with IPA are atypical, however, the patient is critically ill with high mortality. Elevated serum concentration of voriconazole might be more common in severe patients. For those who have a history of systemic application of glucocorticoids, clinical symptoms with hemoptysis, short of breath, radiology with infiltrates, nodular and/or with cavity, and with no response to antibiotics, clinicians should actively seeking evidence of IPA, for early diagnosis, standardized treatment, and improve the prognosis of patients with chronic respiratory diseases complicated with IPA.

To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

Objective: To investigate the impact of aortic root morphology on the implantation depth of aortic valve prosthesis during trans-catheter aortic valve replacement (TAVR) in bicuspid aortic valve patients. Methods: Clinical data of 40 patients with native bicuspid aortic valve stenosis who underwent TAVR using the self-expandable prosthesis (the Venus A-valve) from 2014 to 2017 in Fuwai Hospital was retrospectively analyzed. The patients were divided into non-deep implantation group (implant depth ≤10 mm by instant angiogram after implantation,29 cases) and deep implantation group (implant depth> 10 mm by instant angiogram after implantation,11 cases).Pre-procedural aortic root characteristics (e.g. calcification, angle and dimensions) were assessed by CT. The impact of aortic root morphology on the implantation depth and clinical outcomes were also evaluated. Results: The age was (75.1±5.9) years with equal representation from the raphe-type and non-raphe type (52.5%(21/40) and 47.5%(19/40)).The bigger aorta angle ((56.5±4.5)° vs. (47.4±9.4)°, P=0.004),more frequent mild-calcification (HU850, <200 mm³) or severe-calcification(HU850, >1 000 mm³) of aortic leaflets (7/11 vs. 4/29, P=0.006), as well as higher ratio of left ventricular outflow tract perimeter to annulus perimeter ((109.2±7.5)% vs. (101.5±6.5)%, P=0.004) were found in the deep implantation group compared to the non-deep implantation group. The new in-hospital onset of bundle-branchheart-block or atrioventricular block conduction disturbance rate was higher in the deep implantation group than in the non-deep implantation group (6/11 vs. 2/29, P=0.030).Left ventricular ejection fraction was similar between deep implantation group and non-deep implantation group at baseline((49.9±8.9)% vs. (55.8±10.4)%, P=0.117), and was significantly lower in the deep implantation group than in the non-deep implantation group at 30 days after implantation ((51.6±12.8)% vs. (60.9±8.1)%, P=0.020). Conclusion Aortic root morphology of bicuspid aortic valve patients is associated with implantation depth of the prosthesis during TAVR, which affects the conduction system and left ventricular function during and post TAVR.

Objective The objectives of this study were to investigate the clinical significance of CD39,CD73,double positive subgroups for CD39 and CD73,and other lymphocytes with clinicopathological parameters in the microenvironment of colorectal cancer.Methods Tumor infiltrating lymphocyte(TIL)was collected from 24 patients with colorectal cancer after radical resection.The expression of CD39+,CD73+ or CD39+ with CD73+ in T cells were measured by flow cytometry.The association between these subgroups and clinicopathologic parameters was analyzed.Results The CD73+ and CD39+ with CD73+ subgroups were associated with lymph node metastasis and poor degree of differentiation,and this mechanism was closely related to tumor-associated inflammation.Conclusion CD39+ with CD73+ colorectal tumor infiltration Treg has a more unique biological activity than other Treg group.This study provides a new idea and theoretical basis for predicting the prognosis of colorectal cancer.

This study was aimed to explore the renoprotective effects of Tang-Shen-Ping (TSP) on RhoA/ROCK signaling pathway in KKAy mice with diabetic kidney disease (DKD).A total of 60 female 10-week SPF degree KKAy mice,which were fed with KK special food for 10 weeks,were made into DKD model.Mice were randomly divided in the model group,irbesartan group,low-,medium-and high-dose TSP group (0.525 g· kg-1,1.05 g· kg-1,and 2.1 g· kg-1).Ten female C57BL/6J mice were used as the normal control group.Mice of each group were intragastrically administered with corresponding medicine,respectively,while mice of the control group and the model group were given deionized water of the equal volume.The body weight was measured and the 24-hour urine protein quantification was detected every 4 weeks.At the end of the 26th week,all mice were sacrificed and the biochemical indicators,such as fasting blood glucose (FBG),serum blood urea nitrogen (BUN),serum creatinine (Scr),and triglyceride (TG) were measured.HE staining,Mallory staining and PAS staining were used to observe the pathological morphology of kidney tissues.Immunohistochemistry (IHC) and in situ hybridization (ISH) were used in the detection of transforming growth factor-β1 (TGF-β1),Ras homolog gene family member A (RhoA),Rho-associated coiled-coil-containing protein kinase 1 (ROCK1),α-smooth muscle actin (α-SMA),E-Cadherin (E-Cad) mRNA and protein expression.The results showed that compared with the model group,there were significant differences on body weight,the ratio of kidney weight to body weight,and urinary protein in the middle-and high-dose TSP group (P ＜ 0.01);the renal pathological damage was obviously decreased;contents of FBG,BUN,Scr and TG decreased (P ＜ 0.01);mRNA and protein expression of E-Cadherin increased;mRNA and protein expression of TGF-β1,RhoA,ROCK1 and α-SMA decreased with significant difference in the middle-and high-dosc TSP group (P ＜ 0.01).It was concluded that the renoprotective effects and epithelial-mesenchymal transdifferentiation (EMT) of renal tubular epithelial cells of TSP on DKD KKAy mice may be related to the regulation of RhoA/ROCK signaling pathway.

To study the effect of the Tangshenping containing serum on the proliferation of the high glucose-induced epithelial cells of renal tubules.To prepare durg-contained serum from rats to enter into in vitor reaction system,the cellscultured via 10％ FBS-RPMI 1640 were randomly divided into 7groups:the normal group,themodel group,the Y27632 group,theirbesartangroup,the small dose Tangshenping group,the medium dose Tangshenping group and the high dose Tangshenping group and The cells were cultured in 3000 cells/well and grown in 96-well plates.Each group had 8 wells,then detect the effects of all serum sections on the proliferation of high glucose-induced epithelial cells of kidney tubules by the MTT colorimetric method after cultured for 12 h,24 h,48 h,and 60 h.Based on the results above,cell protein were extracted from each group at 24 h,and the expression of RhoA,ROCK1,α-SMA and E-cadherin in each group were detected by Western blotting.After high glucose stimulation,the shape of cell was shuttle-like or irregular triangle,the way it grew was radial;after the intervention of the corresponding serum,the shape of the cell was fiat and irregular polygonal.Started with 12h,compared with the normal group,OD value of other groups increased;at the 24h、48hand 60h,compared with the normal group,OD value of high glucose groupincreased significantly (P＜0.01);compared with the high glucose group,OD value of treatment groups decreased (P＜0.05);and 48 h,compared with the Y27632group,irbesartan groupand Tangshenping high dose group,OD value of Tangshenping low and medium dose groups decreased (P＜0.05);60 h,compared with Y27632 group,OD value of Tangshenping medium dose groups decreased;compared with irbesartan group,OD value of o Tangshenpinggroupsdecreased (P＜0.05);compared with Tangshenping high dose group,OD value of Tangshenpinglow groupsdecreased (P＜0.05) Western blotting analysis showed that compared with normal group,the expression of E-Cadherin protein in high glucose group reduced,and the expression of RhoA,ROCK1 and α-SMA protein increased;compared with high glucose group,the expression of E-Cadherin protein in each treating group increased,and the Tangshenping large dose group wassignificantly different (P＜0.01);the expression of RhoA,ROCK1 and or-SMA protein reduced,Tangshenping,the large dose group was significantlydifferent (P＜0.01);Compared with the Y27632 group,the expression of E-cadherin,ROCK1 and α-SMA protein in Tangshenping large dose group had no significant difference,while the expression of RhoAproteinreduced (P ＜0.01).Compared with theirbesartan group,the expression of E-cadherin,RhoA,ROCK1 and α-SMA protein in Tangshenping large dose group had no significant difference (P＞0.05).The Tangshenping containing serum is abletoinhibit the proliferation of high glucose-induced epithelial cells of kidney tubules,and can reverse renal tubular-epithelial cell transdifferentiation via regulating RhoA/ROCK signaling pathway,and restrain renal interstitial fibrosis,thereby delaying the pathogenesis of diabetic kidney disease.

Objective:To study the effect of the prescription Tangshenning on the proliferation of the high glucoseinduced cells of near-end kidney tubules.Method:To prepare durg-contained serum from mice to enter into in vitor reaction system,the cells were randomly divided into 4 groups:the normal group,the model group,the,the irbesartan group,the tangshenning group and then detect the effects of all serum sections on the proliferation of high glucoseinduced epithelial cells of kidney tubules by the MTT colorimetric method,and the expression of RhoA,ROCK 1,Ecadherin and α-SMA in each group were detected by Western blotting.Result:The high glucose group of renal tubular epithelial cells form from the flat irregular polygon into long fusiform;After adding the drug-containing serum corresponding intervention into the cells into a flat in irregular polygon.The high glucose group of renal tubular epithelial cells show obvious proliferation condition,In the condition of 24 h,48 h,The high glucose group proliferation is better than the normal group (P＜0.01),in 60 h,The high glucose group proliferation is better than the normal group (P＜0.05);In 24 h,compared with the irbesartan,Tangshenning has better effect of inhibiting the cell proliferation(P＜0.05);In 48 h,Tangshenning has the better effect than irbesartan and Y27632 (P＜0.01);In 60 h,Tangshenning has the better effect than irbesartan and Y27632 (P＜0.05);Western blotting:Western blotting analysis showed that compared with the normal group,the expression of RhoA protein in high glucose group and Y27632 decreased (P＜0.01);The high glucose group and Tangshenning have significant difference (P＜0.01);Y27632 and Tangshenning have difference (P＜0.05).compared with the normal group,the expression of ROCK1 protein in high glucose group decreased (P＜0.01);The high glucose group,Tangshenning,the irbesartan and Y27632 have difference (P＜0.05).Compared with the normal group,the expression of a-SMA protein in high glucose group decreased (P＜0.01);The high glucose group,Tangshenning,the irbesartan and Y27632 have difference (P＜0.05).Compared with the normal group,the expression of E-Cadherin protein in high glucose group increased (P＜0.05).Y27632 and Tangshenning have difference (P＜0.05).The high glucose group,Tangshenning,the irbesartan and Y27632 have difference (P＜0.05).Conclusion:The prescription Tangshenning is able to inhibit the proliferation of high glucose-induced epithelial cells of kidney tubules and and can reverse renal tubularepithelial cell transdifferentiation via regulating RhoA/ROCK signaling pathway,and restrain renal interstitial fibrosis,thereby delaying the pathogenesis of diabetic kidney disease.