[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.

[Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer].

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: （1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

[Comparison of short-term efficacy and perioperative safety between neoadjuvant therapy and total neoadjuvant therapy in patients with locally advanced rectal cancer].

Objective: To compare the short-term efficacy and perioperative safety of neoadjuvant chemoradiotherapy (nCRT) with total neoadjuvant treatment (TNT) in patients with locally advanced rectal cancer (LARC). Methods: A retrospective cohort analysis was carried out. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology with a distance from tumor inferior border to anal verge within 12 cm; (2) clinical stage cT3-4N0 or cT1-4N1-2 diagnosed by magnetic resonance imaging (MRI) or endorectal ultrasonography; (3) a single rectal tumor confirmed by colonoscopy; (4) patients suitable for chemoradiotherapy; (5) no previous history of other tumors. Exclusion criteria: (1)patients with previous rectal cancer surgery and local recurrence; (2) those who did not complete nCRT course; (3) those with distant metastases; (4) those with defective clinicopathological data. According to the above criteria, a total of 134 LARC patients at the Department of General Surgery of Beijing Chaoyang Hospital from January 2016 to January 2019 were enrolled, including 82 males and 52 females, with a male-female ratio of 1.58∶1.00 and mean age of (59.6±11.2) (26-81) years. Based on neoadjuvant regimen, patients were divided into nCRT group (n=55) and TNT group (n=79). There were no statistically significant differences in baseline data, such as age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage, between the two groups (all P>0.05). All the patients received pelvic intensity-modulated radiotherapy (IMRT) with a total dose of 50.4 Gy in 28 fractions. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. Patients in TNT group received one cycle of induction CapeOX (oxaliplatin and capecitabine) and concurrent chemoradiotherapy, then underwent a radical surgery two weeks after completion of consolidation chemotherapy. The efficacy of neoadjuvant therapy, adverse events of chemoradiotherapy and perioperative safety were compared between the two groups. Results: Patients of two groups completed the course of neoadjuvant therapy. There were no statistically significant differences between nCRT group and TNT group in the incidence of adverse events in neutropenia [7.3% (4/55) vs. 10.1% (8/79)], anemia [3.6% (2/55) vs. 3.8% (3/79)], thrombocytopenia [5.5% (3/55) vs. 7.6% (6/79)], gastrointestinal dysfunction [3.6% (2/55) vs. 6.3% (5/79)] and radiation enteritis [9.1% (5/55) vs. 8.9% (7/79)] (all P>0.05). One hundred and thirty patients completed TME surgery, including 54 patients in nCRT group and 76 patients in the TNT group. Compared with the nCRT group, the proportion of abdominoperineal resection (APR) was higher in the TNT group [31.6% (25/76) vs. 13.0% (7/54), χ(2)=9.382, P=0.009]. No statistically significant differences in morbidity of postoperative complication, operation time, intraoperative blood loss and postoperative hospital stay between the two groups were found (all P>0.05). The distal and circumferential margins were negative in all the patients. Seventeen patients in the TNT group 22.4% (17/76) got pathologic complete response (pCR), which was significantly higher than 7.4% (4/54) in nCRT group (χ(2)=5.217, P=0.022). There were no statistically significant differences in ypTNM classification, perineural invasion and venous invasion between the two groups (all P>0.05). Conclusion: The pCR of TNT is higher than that of nCRT without increasing the incidence of toxicity and complications of radiotherapy and chemotherapy for patients with locally advanced rectal cancer.

MiR-182-5p inhibited proliferation and metastasis of colorectal cancer by targeting MTDH.

OBJECTIVE: To investigate the role and molecular mechanism of miR-182-5p in the development of colorectal cancer (CRC), thereby providing a theoretical basis for new CRC therapeutic targets. PATIENTS AND METHODS: The expression of miR-182-5p in CRC clinical cases and biological cell lines was detected. On-line target gene prediction and Luciferase reporter gene assay were performed to screen and verify the target of miR-182-5p, respectively. The role of miR-182-5p in CRC cell function was further analyzed. RESULTS: MiR-182-5p expression was significantly decreased in both CRC tissues and cell lines. Metadherin (MTDH) was screened and verified as a functional target of miR-182-5p. The cell proliferation, invasion and migration ability of CRC cells were significantly inhibited after the up-regulation of miR-182-5p. However, MTDH limited the anti-cancer effects of miR-182-5p in CRC cells. CONCLUSIONS: Our research demonstrated the inhibitory function of miR-182-5p in CRC. Therefore, the miR-182-5p/MTDH axis was expected to be one of the targets of CRC targeted therapy.

[Pulmonary cavities with Takayasu arteritis: report of 3 cases and literature review].

Objective: To analyze the clinical features of 3 cases of Takayasu arteritis(TA) with pulmonary cavities on chest computed tomography(CT). Methods: The clinical data of 3 TA patients with cavities on the chest CT who were admitted into Beijing Chaoyang Hospital were retrospectively analyzed. A literature search was performed with "Takayasu arteritis" and "pulmonary" as the key words in China Knowledge Resource Intergrated Database (CNKI) and Pubmed Database for publications from Jan 1, 2000 to Dec. 31,2017. The relevant literatures were reviewed. Results: Among the 3 patients, 2 were males and 1 was female, aging 49, 28 and 28 years, respectively. They presented with cough, fever and chest pain, and chest CT showed cavities, single or multiple, either with thick or thin wall, or wedge-shaped consolidation, residual stripes after being absorbed, and one case had pulmonary biopsy results which showed hemorrhagic infarction. They were all misdiagnosed before as pneumonia, pulmonary tuberculosis, pulmonary thromboembolism. After being treated by combination therapy of glucocorticoids and immunosuppressive agents, the disease improved significantly. A total of 777 cases with TA involving pulmonary arteries were reported, from which 13 cases with involvement of pulmonary parenchyma were described. Therefore total 16 cases including the 3 cases in this article were included for analysis. Twelve cases showed patchy or wedge-shaped ground-glass opacity and consolidation, and peripheral lung stripes remained after being absorbed. Two cases showed pleural effusion, and 4 cases showed cavities, 3 cases were misdiagnosed as pulmonary tuberculosis, 7 as pulmonary infection, and 5 as pulmonary thromboembolism. Conclusions: TA with pulmonary arteries involved is susceptible to be misdiagnosed and missed, and therefore, in patients with cough, hemoptysis, chest pain and cavities in pulmonary parenchyma, TA should be suspected. Early diagnosis and appropriate treatment can lead to a better prognosis.

[Screening different HPV genotypes infection and type-specific in cervical exfoliated cells of women in Yili area of Xinjiang Uygur Autonomous Region, China].

Objective: To investigate the infection status and genotype distribution of cervical human papillomavirus (HPV) in women of different ethnic groups and different ages in Yili, Xinjiang Uygur Autonomous Region (Xinjiang). Methods: By using the convenient sampling method, 54 760 women from November 2015 to May 2017 seeking for service in gynecological clinics in a general hospital in Yili, Xinjiang, were selected as the research subjects, and 3 445 samples of cervical mucous exfoliative cells were collected, and the social information of their ethnic and age was collected at the same time. The inclusion criteria were those with sexual life, cervical integrity, and ethnic groups for Han or Uygur or Kazak. PCR-reverse dot blot hybridization was used to detect HPV genotyping in exfoliated cells, and chi-square test was used to compare the difference of HPV positive rate among different ethnic groups. Then, according to ethnicity and age, the differences in positive rates of different ages and ethnic groups were compared in each layer. Results: The positive rate of HPV was 25.6% (882 cases), of which the Han, Uygur and Kazakh were 27.9% (564 cases), 22.9% (196 cases) and 21.6% (122 cases), and the difference was statistically significant (χ(2)=13.80, P=0.001). The most prevalent high-risk genotypes of Han women were HPV16/52/58, accounting for 24.8% (140 cases), 17.7% (100 cases) and 9.8% (55 cases), respectively. The most prevalent high-risk genotypes of Uygur women were HPV16/52/53, accounting for 34.2% (67 cases), 12.8% (25 cases), 9.2% (18 cases), respectively. The most prevalent high-risk genotypes of Kazak were HPV16/52/53, accounting for 37.7% (46 cases), 17.2% (21 cases), 12.3% (15 cases), respectively. The highest rate of HPV in Uygur patients aged ≥61 years was 41.5% (22 cases), and the lowest in group 36-40 years old, 15.9% (21 cases), the difference between different age groups was statistically significant (χ(2)=35.01, P<0.001). Conclusion: The positive rate of HPV infection among Han, Uygur and Kazak in Yili Prefecture of Xinjiang was different, and the HPV positive genotype differs among different ethnic groups.

Influence of whole corn feeding on the performance, digestive tract development, and nutrient retention of geese.

The objective of the current study was to investigate the influence of including whole corn (WC) in goose diets on the performance, digestive tract development, and nutrient retention. A total of 112 Yangzhou geese, 7 d old and with similar BW, were distributed into 8 pens of 14 birds/pen (7 male, 7 female). Each treatment was represented by 4 replicates. Geese were fed corn-soybean-based diets containing 640 g (8-28 d) and 615 g (29-70 d) of corn/kg of diet from 8 to 70 d of age, and 2 particle sizes of corn grains were used: ground corn (GC) and WC. During the period from 8 to 49 d, daily feed intake (P < 0.05) and daily weight gain (P = 0.054) of WC-fed birds tended to be lower than that of GC-fed birds. However, WC diet tended to improve (P = 0.07) G:F from 50 to 70 d of age. Higher relative weights of the gizzard (P < 0.05) at 28, 49, and 70 d, proventriculus at 49 d, and duodenum at 28 and 70 d of age were observed in birds fed the WC diet compared with those fed the GC diet. Intestinal wall thickness in the jejunum and crypt depth and intestinal wall thickness in the ileum were greater (P < 0.05) in WC-fed birds at 28 d of age. Villus height and intestinal wall thickness in the duodenum and villus height in the jejunum were greater in birds fed the WC diet compared with those fed the GC diet at 70 d of age, and birds fed the WC diet had a greater (P < 0.05) intestinal wall thickness, villus height, and crypt depth measurements in the ileum compared with those fed the GC diet. The retention ratio of CP and neutral detergent fiber were higher (P < 0.05) in birds fed the WC diet than in those fed the GC diet. Overall, no negative effect was observed in birds fed the WC diet compared with those maintained on the GC diet.

Response of growing goslings to dietary methionine from 28 to 70 days of age.

1. A dose-response experiment with 5 dietary methionine concentrations (23, 33, 43, 53 and 63 g/kg) was conducted with goslings to estimate the growth performance and carcase quality response of growing goslings to dietary methionine from 28 to 70 d of age. 2. A total of 150, 28-d-old birds were randomly distributed to 15 pens with 10 birds per pen according to similar pen weight. There were 5 dietary treatments, each containing three replicate pens. Weight gain, feed intake and feed/gain of goslings from each pen were measured at 2-week intervals from 28 to 70 d of age. At 70 d of age, 4 goslings were selected randomly from each pen and slaughtered to evaluate carcase quality. 3. Significant effects of dietary methionine on daily weight gain (28-56 d) and daily feed intake were determined. Daily weight gain from 28 to 42 d and 28 to 56 d, daily feed intake and gain/feed showed significant quadratic response to increasing dietary methionine, while abdominal fat proportion showed a significant linear response. 4. When dietary CP concentration was 1582 g/kg, the optimal methionine concentrations for growing goslings from 28 to 42 d and 28 to 56 d of age for maximum daily weight gain were 407 and 4.14 g/kg, respectively.

Thiamine deficiency is associated with ethnicity in a subtropical area of China.

Clinical signs which probably indicate thiamine (vitamin B1) deficiency have been evident in the Meng Ding District of Yunnan province, China for decades. In 1990, 5979 people were surveyed using cluster sampling to investigate the association of signs of thiamine deficiency with potential causative factors. Data on past and present symptoms of thiamine deficiency were collected from individual subjects, hospital records and health care personnel. Information on staple food intake over the previous three months was collected from both individual subjects and from commune administrations. Signs of thiamine deficiency occurred most often in the Dai ethnic group. 5.1% of Dai males and 6.6% of Dai females had met criteria for thiamine deficiency at some time over the previous 7 years. In other ethnic groups, signs of thiamine deficiency occurred in only 0. 1% of males and 0.2% of females over the same time period. The incidence of signs of thiamine deficiency did not vary with time during the 7 years prior to the survey, however the condition appeared to be more severe (resulting in more cases of hospitalization) in 1983-1985. Signs of thiamine deficiency showed a seasonal distribution with the highest rates occurring in the hot, dry season. Signs of thiamine deficiency were common among Dai women after childbirth. The findings indicate that thiamine deficiency is strongly associated with ethnicity in this population. It is likely that thiamine undernutrition is associated with dietary intake and practices which differ by ethnic group. Public health measures to minimize thiamine undernutrition in the Dai group include education and supplementation.

[Confidence factors-method for estimating the confidence limits of standardized population rate of indirect method].

The standardized rate of indirect method is widely used, but no method of interval estimation for its population rate has been reported. The authors have discussed the standard error of standardized rate of indirect method and suggested that a method using this standard error should be used to determine the confidence limits for the population rate. In this paper, the authors put forward another method (Confidence Factors-Method) which can be easily applied to determine the confidence limits. It gives approximately the same result with the method mentioned above.