[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

The impact of acute-phase reaction on mortality and re-fracture after zoledronic acid in hospitalized elderly osteoporotic fracture patients.

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

[Analysis of clinicopathological characteristics of non-alcoholic fatty liver disease].

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

[Study on clearance of chlorfenapyr via blood purification (a case analysis)].

This paper analyzed the clinical data of a patient with acute oral emamectin·chlorfenapyr poisoning, and discussed the effect of blood purification therapy on chlorfenapyr poisoning. Chlorfenapyr was detected in the blood, urine, ultrafiltrate and plasma exchange fluid of the patient, and the concentrations of chlorfenapyr poison gradually decreased with time. Blood purification has a certain effect on chlorfenapyr, and early blood purification may be an effective measure to treat chlorfenapyr poisoning.

A review of micronutrient deficiencies and analysis of maize contribution to nutrient requirements of women and children in Eastern and Southern Africa.

This paper reviews and analyses the importance of maize as staple food in Eastern and Southern Africa (E&SA) and contributes in understanding the nexus between maize nutritional composition and prevalence of micronutrient deficiencies (MNDs) in these regions. MNDs remain a major public health concern particularly for women and children, with calcium, iodine, iron, selenium, zinc, folate and vitamin A deficiencies being the most common. Estimates of their prevalence are among the highest in E&SA: iron-deficient anemia affected 26 to 31% of women of reproductive age, and deficiencies up to 53%, 36%, 66%, 75% and 62% for vitamin A, iodine, zinc, calcium and selenium, respectively, were measured in populations of these regions. Besides, these two regions show the highest worldwide maize per capita consumption (g/person/day) as main staple, with 157 in Eastern Africa and 267 in Southern Africa, including up to 444 in Lesotho. The analysis of food composition tables from these regions showed that 100 g of maize foods consumed by these populations could to some extent, contribute in satisfying dietary reference intakes (DRIs) of children and women in energy, proteins, carbohydrates, magnesium, zinc, vitamins B1 and B6. However, it provides very low supply of fats, calcium, sodium, selenium, vitamins C, A and E. The high occurrence of MNDs and considerable nutritional potential of maize consumed in E&SA can be explained by loss of nutrients due to processing practices, low food diversification and reduced nutrients bioavailability. Success cases of the main strategies to tackle the issue of MNDs in these regions by improving maize nutritional quality are discussed in this paper. Maize fortification was shown to improve nutrition and health outcomes of population. Increasing dietary diversity by complementing maize with other foods has improved nutrition through integration of micronutrient-rich foods in the diet. Mostly, biofortification has successfully contributed in reducing vitamin A and zinc deficiencies in rural communities more than nutrient supplementation, fortification and dietary diversity.

Association between built environments and quality of life among community residents: mediation analysis of air pollution.

OBJECTIVES: The aim of this study was to analyze the relationship between built environments and quality of life (QoL), and the mediating role of air pollution in that relationship. STUDY DESIGN: This was a cross-sectional population-based study. METHODS: Data of 5196 adults residing in 148 communities in three cities in Liaoning Province, China, were analyzed. Objective measures of traffic design included street connectivity, road network density, bus station density, and parking lot density; residential greenness was controlled as a confounder. QoL was evaluated using the 12-Item Short Form Health Survey. The average concentrations of PM2.5 and SO2 one month before QoL collection for each community were calculated. RESULTS: Road network density and parking lot density were negatively associated with the Physical Component Summary (PCS), but street connectivity was positively associated with PCS for the participants. Bus station density, street connectivity, and parking lot density were negatively associated with the Mental Component Summary (MCS), and PM2.5 and SO2 mediated this association. In addition, gender and road network density and parking lot density had an interactive effect on the MCS of the participants. CONCLUSIONS: Dense traffic affects people's health not only directly but also indirectly through air pollution. The effects of built environments and air pollution should be considered when building healthy, supportive communities, and healthy cities.

[Kindlin-2 regulates endometrium development via mTOR and Hippo signaling pathways in mice].

OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool mice and Kindlin-2flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. RESULTS: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. CONCLUSION: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.

[Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen].

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

[Correlation of VISTA and PD-L1 expression with the clinicopathological features and prognosis in triple-negative breast cancer].

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8+T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Association between air pollution and atopic dermatitis in Guangzhou, China: modification by age and season.

BACKGROUND: The short-term effect of ambient air pollution on atopic dermatitis (AD), along with its effect modifiers, has not been fully addressed. OBJECTIVES: To examine the short-term associations between air pollution and AD, and to identify effect modifications by age and season. METHODS: We used the generalized additive model to evaluate the short-term effect of ambient air pollution on daily hospital visits for AD, adjusting for potential confounders. Subgroup analyses were performed to identify potential effect modifications by season and age (< 18 years and ≥ 18 years). RESULTS: A total of 29 972 hospital visits for AD were recorded in Guangzhou, China, from 19 January 2013 to 31 December 2017. Among them, 72·8% were visits by children and 51·4% occurred in the cool season. Acute and delayed effects on AD hospital visits were significant for all air pollutants. Stronger effects were seen in the cool season (approximately 1·7-3·0 times higher than effects in the warm season). Stronger effects were also observed in children (approximately 1·3-1·8 times higher than effects in adults). Sensitivity analyses indicated the results were robust. CONCLUSIONS: Air pollution might be an important trigger for AD in subtropical Guangzhou, China. Children are more vulnerable than adults, and the effects are stronger in the cool season.

Maintenance of cellular annexin A1 level is essential for PI3K/AKT/mTOR-mediated proliferation of pancreatic beta cells.

Annexin A1 (AnxA1, also known as lipocortin-1), is a calcium-dependent phospholipid binding protein with diverse functions. Previous studies have indicated that AnxA1 is associated with age-related ß-cell dysfunction and aging, which lead to decreased ß-cell proliferation capacity. However, it has been uncertain whether AnxA1 affects the proliferation of pancreatic beta (ß) cells. In the present study, we reduced AnxA1 expression in the MIN6 islet ß-cell line using small interfering RNA (AnxA1-siRNA), then measured cell cycle distribution and cellular proliferation. We also measured the expression levels of cell cycle-related proteins such as cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2) by Western blot analysis. We investigated the phosphatidylinositol 3-kinase (PI3K)/ serine/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway to explore the potential mechanism underlying the observed effects. Knockdown of AnxA1 expression using siRNA reduced the rates of MIN6 cell proliferation. The proportions of cells in S and G2/M phases also decreased upon inhibition of AnxA1. Moreover, AnxA1 protein expression in MIN6 cells was positively related to the protein levels of cyclin D1, cyclin E, and CDK2. Activation of the PI3K/Akt/mTOR signaling pathway by AnxA1 may be involved in the signaling cascade to regulate cell proliferation. This study identified a positive correlation between AnxA1 protein and pancreatic ß-cell proliferation. AnxA1 protein expression might affect the proliferation of MIN6 cells via regulation of cyclin D1, cyclin E, and CDK2 proteins, as well as the PI3K/Akt/mTOR signaling pathway.

Association of metabolic syndrome with cardiovascular outcomes in hypertensive patients: a systematic review and meta-analysis.

PURPOSE: The association between metabolic syndrome (MetS) and cardiovascular outcomes in patients with hypertension is still controversial. This meta-analysis sought to evaluate the association of MetS with cardiovascular outcomes in hypertensive patients. METHODS: Two authors comprehensively searched PubMed and Embase databases from their inception to April 18, 2020 for the longitudinal studies that evaluated the association of MetS with cardiovascular outcomes in patients with hypertension. The main outcomes were major adverse cardiovascular events (myocardial infarction, revascularization, stroke, hospitalization due to heart failure, etc.) and stroke. RESULTS: Eight studies consisting of 36,614 hypertensive patients were identified and analyzed. Meta-analysis indicated that MetS was associated with an increased risk of major adverse cardiovascular events (risk ratio [RR] 1.55; 95% confidence intervals [CI] 1.28-1.87), cardiovascular mortality (RR 1.44; 95%CI 1.13-1.82), and stroke (RR 1.46; 95%CI 1.22-1.75), respectively. Sensitivity analysis further confirmed the robustness of the prognostic value of MetS. CONCLUSIONS: MetS is associated with higher risk of major adverse cardiovascular events, cardiovascular mortality, and stroke in patients with hypertension. Determination of MetS may contribute to improving cardiovascular risk stratification in hypertension.

[Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm].

Objective: To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions. Methods: The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding. Results: A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group (P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm (OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion (OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions: The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

[Identification of the feature of immune cells infiltration in inherited renal carcinoma with von Hippel-Lindau syndrome].

Objective: To investigate the feature of immune cells infiltration in inherited renal carcinoma with von Hippel-Lindau (VHL) syndrome and their relationship with clinicopathological characteristics and prognosis. Methods: The samples were collected from patients with VHL syndrome renal carcinoma who were diagnosed and treated surgically at the Department of Urology, Peking University First Hospital from 2010 to 2019. RNA-Seq was performed on 6 pairs of VHL syndrome renal carcinoma and adjacent normal tissues. To identify the specific infiltrated immune cells, RNA-Seq data was converted into the infiltration data of 14 types of immune cells using the TIP tool. Immunohistochemical staining was used to verify the expression of the markers of these specific infiltrated immune cells in the paraffin sections of 54 paired VHL syndrome renal carcinoma and adjacent normal tissues, and to analyze their relationship with clinicopathological characteristics and prognosis. Results: Compared with adjacent normal tissues, CD4 Naive infiltration level was significantly down-regulated (0.289±0.009 vs 0.200±0.012,P<0.001) and CD4 Memory infiltration level was significantly up-regulated (0.123±0.014 vs 0.222±0.016,P<0.001) in VHL syndrome renal carcinoma. Immunohistochemical staining results showed that CD45RA (a CD4 Naive cell marker) expression was significantly reduced (50.9±1.9 vs 15.6±0.9,P<0.001) and CD45RO (a CD4 Memory cell marker) expression was significantly increased (22.2±1.1 vs 80.8±4.3,P<0.001) in VHL syndrome renal carcinoma. Besides, lower CD45RA expression and higher CD45RO expression were associated with higher histological grade, advanced tumor stage and shorter disease-free survival (all P<0.01). In addition, CD45RA expression was positively correlated with VHL expression (r=0.693 3, P<0.000 1) and CD45RO expression was negatively correlated with VHL expression (r=-0.609 0, P<0.000 1). Conclusions: This study found that CD4 Naive and CD4 Memory cells may be differentially infiltrated immune cells in VHL syndrome renal carcinoma, and their infiltration levels were associated with the expression of VHL and the prognosis of patients.

[Clinicopathological and prognostic characteristics of clear cell papillary renal cell carcinoma].

Objective: To analyze the epidemiological, clinicopathological and prognostic characteristics of clear cell papillary renal cell carcinoma (CCPRCC) based on Chinese patient population. Method: Patients with renal cell carcinoma diagnosed at Peking University First Hospital from June 2016 to June 2020 were included in this study based on the inclusion and exclusion criteria. All cases were grouped according to CCPRCC, clear cell renal cell carcinoma (ccRCC), and papillary renal cell carcinoma (pRCC), and the general clinical, postoperative pathological and follow-up data of the patients were retrospectively analyzed. Result: A total of 18 CCPRCC patients were enrolled in this study, accounting for 0.44% (18/4 110) of the postoperative pathologically confirmed renal cell carcinoma cases in our hospital during this time period. The age range of the included patients was 28-86 years old, with a median age of 49.5 years old. There were 11/18 males and 7/18 females. All CCPRCC patients had no family history of renal malignant tumors. Among them, only one patient with CCPRCC had related clinical symptoms, that was intermittent waist and abdomen pain, while the other 17 cases were found by physical examination without any related symptoms. Compared with ccRCC and pRCC, there was no significant difference in their end stage renal disease history(χ2ccRCC=0.291, χ2pRCC=1.161,all P>0.05). The maximum diameter of CCPRCC tumor was smaller than pRCC (χ2=-2.280,P =0.027) but not significantly different from ccRCC (χ2=-0.579,P =0.565). The majority of patients with CCPRCC were in pT1, their pathological stage was earlier than the other two types, and their overall survival was better than ccRCC and pRCC (P<0.05). Conclusion: CCPRCC is a type of renal cell carcinoma with unique epidemiology, clinicopathology and prognostic characteristics. Patients with this subtype have an earlier clinical stage and a better prognosis than ccRCC and pRCC.

[The relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients].

Objective: Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients. Methods: Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-ß2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ2-trend test and verified by logistic regression. Results: The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group (Z=7.685, χ²=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-ß2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ²=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-ß2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions: In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-ß2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

[Etiological survey and traceability analysis of five cases of typhoid fever during the same period in Yantai city].

Objective: To analyze the etiological characteristics and molecular epidemiological correlation of five cases of typhoid fever during the same period in yantai city. Methods: Six S. Typhis strains were isolated from 5 typhoid patients and epidemiological samples in Yantai city in 2018. The onset time of the cases were from May 26, 2018 to July 24, 2018, distributed in Shuidao Town of Muping District, Dengzhou Street of Penglai District, Donglai Street of Longkou District, Wenhua Street of Muping District and Fulaishan Street of zhifu District. S. Typhis strains were analyzed by conventional bacterial isolation method and XbaⅠ/BlnⅠ double-enzyme digestion pulse-field gel electrophoresis (PFGE). Meanwhile, ViaB virulence gene detection and 27 common antibiotics sensitivity tests were conducted to study the etiology of S. Typhis. Results: Six strains of S. Typhi were isolated from 5 patients and the domestic egg of one patient, which were divided into 4 PFGE patterns by PFGE-XbaⅠ and PFGE-BlnⅠ and among which 3 strains had the same PFGE patterns.One multi-drug resistant strain (foreign patient), one single-drug resistant strain (patient with a history of provincial retention), and one completely sensitive strain were detected. The three strains of the same PFGE pattern exhibit the same drug-sensitive phenotype which were intermediate against aminoglycosides and quinolones and susceptibility against the other antibiotics.All of the strains carried the ViaB virulence factor except the strain from the foreign patient. Conclusion: Local S. Typhi is susceptibility or intermediate against antibiotics commonly used in clinic.Sporadic cases of typhoid fever and typhoid imported infections still need attention.

[Relationship between clinicopathological features and prognosis of pancreatic ductal adenocarcinoma].

Objective: To investigate the relationship between clinicopathologic features and prognosis of pancreatic ductal adenocarcinoma located in the head of pancreas. Methods: A retrospective study was performed on 169 patients undergoing radical resection for pancreatic head cancer collected in the First Affiliated Hospital with Nanjing Medical University from January 2018 to April 2019. Univariate analysis and multivariate analysis were performed. Results: Patient's age, tumor differentiation, tumor maximum diameter, resection margin (several resection margins including portal vein groove resection margin, posterior resection margin, and uncinate resection margin), number of positive lymph nodes, number of regional lymph node dissected, and some preoperative and postoperative indicators were associated with prognosis (P<0.05). Direct tumor invasion of organs and surrounding tissues, perineural and vascular invasion, pathologic variants etc. had no statistical significance for survival time. Patient's age, maximum tumor diameter, degree of differentiation, uncinate incision margin, number of regional lymph nodes dissected, and preoperative CA19-9 were independent factors affecting prognosis. Patients older than 74 years of age, with tumors larger than 3 cm in diameter, poorly differentiated, less than 7 regional lymph node dissected, positive uncinate margin, and preoperative CA19-9 higher than 1.5×105 U/L were independent risk factors in patients with pancreatic head cancer. Conclusions: Old age, tumor lager than 3 cm, poor differentiation, low examined lymph nodes, direct uncinate margin involvement and (or) with preoperative CA19-9 higher than 1.5×105 U/L are related to poor prognosis of head pancreatic cancer.