Renal functional compensation after unilateral radical nephrectomy of renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate factors influencing renal functional compensation(RFC) of the preserved kidney after radical nephrectomy (RN).@*METHODS@#A total of 286 patients treated with RN in Peking University People's Hospital were retrospectively analyzed. Preoperative body mass index (BMI), systolic blood pressure (SBP), history of smoking, history of chronic diseases and other basic information, as well as preoperative blood biochemistry, urine routine, imaging examination results were recorded. All the patients underwent 99mtechnetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) renal scans before operation. The surgical method, pathology and blood creatinine values from 1 month to 60 months after RN were recorded. Preoperative and postoperative estimated glomerular filtration rate (eGFR) was calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Renal functional compensation was defined as percent change in eGFR of the preserved kidney after RN compared with the preoperative eGFR. Univariate and multivariate regression analyses were used to identify predictive factors of RFC.@*RESULTS@#Median age was 61 years and 65.4% of the patients were male. Early stage (T1 or T2) tumors were found in 83.6% of the cases. 18.5% of the patients had preoperative diabetes mellitus, 39.5% had hypertension, 19.2% had a history of smoking, and 27.6% were found to have renal cyst on the contralateral side. In the study, 226 cases underwent laparoscopic radical nephrectomy and 60 cases underwent open radical nephrectomy. Renal clear cell carcinoma was the most common pathological type, accounting for 88.5%. The median tumor maximum diameter was 4.5 cm (0.7-13.5 cm). Median renal function compensation was 27% one month after radical nephrectomy. Functional stability was then observed to 5 years. The results of univariate analysis showed that age, gender, preoperative blood uric acid, preoperative urine protein, contralateral renal cyst, and percentage of split renal function of contralateral kidney were correlated with RFC (P < 0.05). Among them, UA level and split renal function of contralateral kidney were strongly negatively correlated with RFC. The results of multivariate linear regression analysis showed age (P < 0.001), blood uric acid (P < 0.001), urine protein (P=0.002), preoperative eGFR (P < 0.001) and the split renal function of contralateral kidney (P < 0.001) were independent predictors of RFC.@*CONCLUSION@#The basic examinations, such as blood biochemistry, urine routine and renal scan before RN are of great significance in predicting the compen-satory ability of the preserved kidney after RN, which is supposed to be taken into consideration when making clinical decision.

Clinical and pathological analysis of small renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical and pathological features of small renal cell carcinoma (RCC), especially of those with diameter less than 4 cm and to understand the characteristics and factors related to recurrence and progression.@*METHODS@#A total of 200 patients with RCC were stratifiedly selected for retrospective analysis. Their baseline demographic features, tumor-specific clinical features, pathological features of renal lesions, especially microscopic features were collected. The patients were divided according to the largest diameter of renal tumor lesions. Univariate analysis was used to compare the differences between tumor staging and microscopic pathological features between the groups. Binary multivariate Logistic regression was used to investigate factors related to tumor progression and prognosis in the patients with small RCC.@*RESULTS@#The tumor diameters of 127 RCC patients were less than 4 cm and most of them had clear cell renal cell carcinoma (ccRCC). The increase in tumor diameter resulted in significantly higher T stage (P<0.01), higher WHO/International Society of Urological Pathology (ISUP) grade (P<0.05) and increasing chance of lymph node metastasis (P<0.01). Even when the tumor diameter was less than 4 cm, the patients might still have perirenal fat invasion, renal sinus invasion and greater elevated tumor grade (greater than grade 3) and synchronous lung metastasis. The incidences of intravascular thrombus (9.3% vs. 0) and tumor necrosis (27.8% vs. 5.5%) in the patients with RCC between 4-7 cm were significantly higher than those with RCC less than 4 cm (P<0.01). Sub-group analysis of small RCC (less than 4 cm) indicated that the patients with RCC between 2-4 cm were more likely to have intratumoral hemorrhage (44.7% vs. 23%, P<0.05) and necrosis than those with RCC less than 2 cm (8.2% vs. 0, P=0.095). Logistic regression analysis of small RCC showed that the incidence of tumor invasion to renal capsule was higher in ccRCC (OR=5.15, 95%CI: 1.36-19.52). Necrosis was closely related to the formation of peritumor pseudocapsule in small RCC (OR=14.90, 95%CI: 1.41-157.50). Increase in the tumor diameter was related to higher tumor grade (greater than grade 3) (OR=3.49, 95%CI: 1.11- 10.93).@*CONCLUSION@#The tumor stage and grade of small RCC (less than 4 cm) are low, but extra-renal invasion and synchronous distant metastasis may occur. Internal hemorrhage and necrosis in tumor, ccRCC subtype, along with microscopic features, such as the renal capsule invasion and perirenal pseudocapsule formation are relevant factors of malignant behavior of small RCC and could be considered in prognosis evaluation.

Application of a novel porous tantalum implant in rabbit anterior lumbar spine fusion model: in vitro and in vivo experiments / 中华医学杂志(英文版)

BACKGROUND@#Some porous materials have been developed to enhance biologic fusion of the implants to bone in spine fusion surgeries. However, there are several inherent limitations. In this study, a novel biomedical porous tantalum was applied to in vitro and in vivo experiments to test its biocompatibility and osteocompatibility.@*METHODS@#Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured on porous tantalum implant. Scanning electron microscope (SEM) and Cell Counting Kit-8 assay were used to evaluate the cell toxicity and biocompatibility. Twenty-four rabbits were performed discectomy only (control group), discectomy with autologous bone implanted (autograft group), and discectomy with porous tantalum implanted (tantalum group) at 3 levels: L3-L4, L4-L5, and L5-L6 in random order. All the 24 rabbits were randomly sacrificed at the different post-operative times (2, 4, 6, and 12 months; n = 6 at each time point). Histologic examination and micro-computed tomography scans were done to evaluate the fusion process. Comparison of fusion index scores between groups was analyzed using one-way analysis of variance. Other comparisons of numerical variables between groups were made by Student t test.@*RESULTS@#All rabbits survived and recovered without any symptoms of nerve injury. Radiographic fusion index scores at 12 months post-operatively between autograft and tantalum groups showed no significant difference (2.89 ± 0.32 vs. 2.83 ± 0.38, F = 244.60, P = 0.709). Cell Counting Kit-8 assay showed no significant difference of absorbance values between the leaching liquor group and control group (1.25 ± 0.06 vs. 1.23 ± 0.04, t = -0.644, P = 0.545), which indicated the BMSC proliferation without toxicity. SEM images showed that these cells had irregular shapes with long spindles adhered to the surface of tantalum implant. No implant degradation, wear debris, or osteolysis was observed. Histologic results showed solid fusion in the porous tantalum and autologous bone implanted intervertebral spaces.@*CONCLUSION@#This novel porous tantalum implant showed a good biocompatibility and osteocompatibility, which could be a valid biomaterial for interbody fusion cages.

Clinical and pathological analysis of renal cell carcinoma bone metastasis / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical and pathological characteristics of renal cell carcinoma bone metastasis (RCC-BM) patients.@*METHODS@#Data of RCC-BM patients from July 2003 to November 2017 were retrospectively reviewed. The patients' baseline characteristics (age, gender), tumor characteristics [specific sites of bone metastasis, time to bone metastasis (TTBM), imaging features of bone disease, coexistence of other metastasis], as well as pathological features (histological classification of primary and bone metastasis, immunohistochemical stain results) were collected. Descriptive analysis and difference analysis were used.@*RESULTS@#A total of 113 RCC-BM patients were enrolled with the gender ratio (male:female) of 4:1, mean age of 59.39 years, and all present of osteolysis bone lesions. The common sites of bone metastasis were vertebra (46.0%) and pelvis (38.9%). Other distant metastasis sites coexisted in 28.3%, while 48.18% RCC-BM patients presented with synchronous metastasis (TTBM=0). The median TTBM for metachronous metastasis was 48 months. The majority in this cohort were determined to have primary tumor of clear cell carcinoma. After immunohistochemical examination to 104 RCC-BM patients and sub-group analysis, tendencies of higher positive rates of vascular endothelial growth factor (VEGF) was also found in synchronous group (P=0.097) while tendencies of higher positive rates of carbonic anhydrase (CA)-IX was found in the same group (P=0.100). The patients with clear cell RCC-BM had a significantly higher positive expression of epithelial growth factor receptor (EGFR, P<0.05) than those with non-clear cell RCC-BM group.@*CONCLUSION@#More male and younger patients with metastatic lesions in axial skeleton were found in this cohort. Tendencies in the expression of CA-IX and VEGF in different TTBM sub-group and EGFR in different histology-derived subgroup indicate that they might be associated with risk and prognostic factors and support further target therapies of RCC-BM.

Renal mucinous tubular and spindle cell carcinoma combined with multiple bone metastasis: a case report and literature review / 北京大学学报(医学版)

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare sub-type of renal cell carcinoma (RCC). It has been considered to be a kind of "indolent" tumor with low-grade fashion, weak invasive capacity and relatively favorable prognosis. However, in the current case, a 3.7 cm×2.8 cm spherical mass with contrast enhancement was found in the left kidney incidentally by computed tomography (CT) in a 60-year-old male patient. A lesion in the right humerus (2.1 cm×1.6 cm×3.1 cm) was found at the same time without any symptoms or sign of pathological fracture by magnetic resonance (MR) imaging. Further positron emission tomography (PET)/CT scan which was ordered immediately after admission suggested multiple bone destruction including skull, pelvis, sternum, right humerus and femur, left scapula, multiple vertebrae and libs. Pathological examination after radical nephrectomy and palliative resection with internal fixation of the lesion in the right humerus indicated that both renal (3.0 cm×3.0 cm×2.5 cm) and bone lesions were MTSCC with the features of high-grade ovoid epithelioid cells, cord-like spindle cells and mucinous matrix under light microscope. The diagnosis of renal MTSCC concurrent with multiple bone metastasis was made. This case report suggested the necessity of general evaluation, especially bone scan for possible distant metastasis, as MTSCC might present unexpected advanced behaviors without any orthopedic symptoms. The behavior of bone metastasis might be associated with male and elderly age. MTSCC has similar enhancement features to papillary RCC on CT scan. As results, attentions are needed to differentiate MTSCC from papillary RCC as they both tend to show lesser enhancement degrees than cortex. Rather than exhibiting a dedifferentiating appearance, the pathological characteristics of bone metastasis lesion were close to those of primary renal lesion. The reason of distant metastasis to the bone remained unclear, negative expression of cytokeratin (CK) 7 might be attributed to. Though immunotherapy, chemotherapy and target therapy could all be methods for systematic therapies, procedures to remove renal lesions and prevent skeletal related events are still highly recommended.

Epidemiological characteristics and spatial-temporal clustering analysis on pulmonary tuberculosis in Changsha from 2013 to 2016 / 中南大学学报(医学版)

To analyze the epidemic characteristics and to explore the spatial-temporal clusters of pulmonary tuberculosis (PTB) in Changsha from 2013 to 2016.
 Methods: Descriptive analysis and space-time permutation scan statistic were used to analyze the reported PTB cases in Changsha from 2013 to 2016.
 Results: Between 2013 and 2016, a total of 17 721 PTB cases were reported in Changsha, with annual reported incidence rate at 60.87 per 100 000 population. Males and individuals aged 15 to <60 years accounted for higher proportion of PTB cases compared to females and other age groups. The number of reported PTB cases reached peak from March to May in each year. The space-time permutation scan statistic identified one most likely cluster and two secondary clusters of PTB cases. The most likely cluster covered most areas of Liuyang City and the North-east part of Changsha County from October 1, 2013 to February 28, 2014. The first cluster occupied 12 towns (streets) in Kaifu District and Changsha County in December 2016. The second cluster included four towns (streets) in Yuhua District and Tianxin District from March 1 to September 30, in 2013.
 Conclusion: Between 2013 and 2016, significant space-time clusters of PTB cases were identified in Changsha. These findings could provide a guide for development of regional intervention strategies for PTB control.

Risk factors and prophylactic strategies of hepatitis B virus vertical transmission / 上海预防医学

Chronic hepatitis B virus ( HBV) infection is a principal risk factor for liver cirrhosis and hepatocellular carcinoma in China , representing one of the major public health problems .Horizontal trans-mission of HBV in vaccinated children was greatly reduced due to widespread HBV vaccination in mainland China, which had limited effects on vertical transmission .Thus, vertical transmission became one of the main causes of HBV chronic infection .High HBV load (≥10 6 copies/mL ) and hepatitis B e antigen ( HBeAg )-positivity in maternal peripheral blood were independent risk factors for HBV intrauterine infection .Compared to HBV infection in early childhood and in adult , intrauterine HBV infection was more prone to developing chronic infection .To decrease vertical transmission of HBV , we recommend that young pregnant women with sero-positive for HBeAg and high serum HBV DNA level should receive antiviral treatment with nucleotide analogues since the 28 th gestation weeks .For newborns born to HBeAg-positive mother , hepatitis B immunoglobulin ( HBIG ) injection should be administrated in combination with HBV vaccination .

Study on risk factors in trans-placental transmission of hepatitis B virus / 上海预防医学

Objective] To study hepatitis B virus ( HBV) mother-to-child transmission and the impact factors, providing the basis for preventive strategies. [ Methods ] A total of 154 hepatitis B surface antigen ( HBsAg ) -positive pregnant women and 297 HBsAg -negative pregnant women from Baoshan District Centers for Disease Control and Prevention in Shanghai were enrolled and received an epidemiological survey regarding mother-to-child transmission.Mothers'peripheral blood and newborns'cord blood were collected to be tested for HBV serological markers and HBV DNA load.HBsAg positivity and HBV DNA≥103 copies/mL in cord blood of newborns born of HBsAg-positive mothers was defined as trans-placental HBV transmission. [ Results] The trans-placental transmission rate was found to be 8.4%for HBsAg-positive mothers.Trans-placental transmission rate was significantly higher among both HBsAg and HBeAg -positive women compared to those only with HBsAg -positiveness ( 20.0% vs. 3.7%, relative risk was 5.41, P <0.05), and increased with HBV DNA load in mothers'peripheral blood. [ Conclusion] HBeAg can directly transmit through the placenta, while HBsAg is“filtered” to a certain degree.HBeAg positiveness and high HBV DNA load of the mother are risk factors in trans-placental transmission, and possibly lead to the failure of newborn immunoprophylaxis.

Impact of viral genotypes and their mutations on the occurrence of hepatocellular carcinoma among HBV infected patients：a cohort study / 上海预防医学

Objective] To investigate the relationship between hepatitis B virus( HBV) genotype and their mutations on the development of hepatocellular carcinoma ( HCC ) . [ Methods ] A cohort study on patients with chronic HBV infection was followed up.HBV genotypes were identified by nested multiplex PCR and multiplex PCR.And HBV mutations in the basic core promoter region were sequencing by PCR amplification. [ Results] The patients infected with genotype B were followed up for an average of 8.52 years (IQR:6.67-10.75), of whom the incidence of HCC was 6.55/1 000 person-years.After follow up with an average of 8.87 years (IQR:6.85-11.33), the incidence of HCC was 11.63/1 000 person-years for the patients infected with genotype C, which were significantly higher than those infected with genotype B (P=0.006).In genotype B HBV infected patients, age (≥60 years), cirrhosis can in-crease the risk of HCC, and in genotype C patients, male, age (≥40 years), cirrhosis, C1653T, T1753V, A1762T/G1764A mutation as well.Interferon therapy can reduce the risk of HCC.In genotype C group, interferon treatment reduced HCC risk in patients carrying A1762T/G1764A mutation (HR=0.21, P=0.008) and in those without T1753V ( HR=0.08, P=0.012) and C1653T mutation ( HR=0.17, P=0.013). [Conclusion] HBV genotypes and mutation are closely associated with HCC.Patients infected with genotype C, carrying 1762T/G1764A mutation should be given priority of receiving antiviral treatments in order to prevent HCC;those carrying C1653T or T1753V mutation should be monitored closely to detect early HCC and receive timely surgical resection.

Current situation and training needs of disaster medicine-related knowledge in community-based populations in Yangpu district of Shanghai / 上海预防医学

Objective] To explore disaster response capability and the vulnerability as well as the current level and training needs of disaster medicine knowledge in urban populations . [ Methods] Five communities in Yangpu District of Shanghai were randomly enrolled in this study .The study populations were then stratified by age groups .A total of 1700 residents were recruited , 1643 of which completed a structured questionnaire designed by the investigators . [ Results] Eight-nine percent of the residents be-lieved the importance of understanding disaster medicine -related knowledge .The correct answer rates of “pro-tective measures of nuclear leakage issues” and “self-rescue measures in a high building fire” reached over 80%;however , the overall correct answer rate of “cardiorespiratory resuscitation operation” was less than 40%.The main channels of community residents accessing disaster medicine knowledge were mainly news -papers, magazines, and internet (52.1%);whereas only 5.3%of them obtained the knowledge from school education .Community residents most liked to obtain “first aid skills”and“basic theory of disaster medicine”through formal lectures (72.4%). [Conclusion] School education lacks disaster-related knowledge , pos-sibly resulting in the fact that community residents have a limited ability to save both oneself and others in disaster .There are significant differences between residents with different education levels .Community resi-dents have limited knowledge of disaster occurrence and development , and lack capabilities of self-rescue and mutual aid .Colleges should increase the contents of disaster medicine education in their curriculum .Disaster education should be enforced in school education .Continued education and simulation of disaster-related knowledge should be regularly offered to community residents to greatly reduce their vulnerability to disasters .

Role of hepatitis B virus mutation, somatic mutations of hosts and related immune genetics in liver cirrhosis and hepatocellular carcinoma / 第二军医大学学报

Hepatitis B virus (HBV) infection has always been one of the most important public health issues in mainland China, causing a huge disease burden. It often takes decades for the chronic process of malignant transformation from HBV infection to different stages of liver diseases. Mutations associated with virus survival are eventually selected by the chronic infection process and under the immune pressure of host. These selected HBV mutations further promote the malignant transformation of liver diseases. A large amount of somatic mutations are produced in the HBV-related chronic inflammatory micro-environment, and those survival-related mutations will then be selected. The selected HBV mutations and host somatic mutations work together to promote the malignant transformation, which can be termed as an evolutionary process of “mutation-selection-adaptation”. In addition, genetic variations of individual hosts also play an important role in HBV related disease progression. For example, single-nucleotide polymorphisms of STAT pathway and HLA can interact with important HBV mutations and therefore affect HBV-related disease progression.

Strategies for exome sequence data analysis for discovering genes underlying autosomal recessive disorders / 中华医学遗传学杂志

Introduced in 2009, whole-exome sequencing (WES) is a technology in which target capture methods are used to enrich sequences of coding regions of genes from fragmented total genomic DNA, which is followed by high-throughput sequencing of the captured fragments. As reported, WES has been successfully applied for discovering genes underlying several Mendelian diseases, especially autosomal recessive types. In this review, authors have summarized the main computational strategies which have been applied to identify novel autosomal recessive diseases genes using whole-exome data.