National Medical Journal of China
Volume 101 · Issue 46 · 2021
Natl Med J China
The prevalence of renal cell carcinoma is increasing in recent years. With the development of research, we know more about the mechanism and biological characteristics of renal cell carcinoma. Currently, the most used prognosis evaluation methods are clinical factors based prognostic prediction models. New drugs, typified by the checkpoint inhibitors, have achieved great success in the treatment of renal cell carcinoma, on the basis of traditional tyrosine kinase inhibitor. With recognition of more prognosis and treatment related biomarkers, directive role for the prognosis prediction and treatment options could be expected.
The lower temperature in autumn-winter provides favorable conditions for the survival and spread of respiratory infectious diseases such as the corona virus disease 2019 (COVID-19) and influenza. It is likely that there will be a co-circulation of respiratory pathogens such as SARS-CoV-2 and influenza. In order to promote the prevention and control of influenza and the application of influenza vaccination during the COVID-19 pandemic in China, we separately discussed the risk of influenza epidemic in the 2021-2022 season, the influenza vaccination policies, and advocate influenza vaccination during the COVID-19 pandemic from the perspective of population medicine. We appeal that COVID-19 vaccination cannot delay the normal delivery of other vaccines in the national immunization programs and non-Expanded Program on Immunization (EPI) vaccines. Promoting influenza vaccination policies and improving immunization service convenience are necessary for increasing influenza vaccine coverage, protecting public health and assisting COVID-19 response.
This paper introduced several problems of long-term oxygen therapy in chronic obstructive pulmonary disease (COPD) patients, including basic concepts, research progress at home and abroad, physiological significance of long-term oxygen therapy, clinical indications, contraindications, long-term oxygen therapy under special conditions, oxygen source, connection mode, inhaled oxygen concentration management, airway humidification, cooperation and safety of non-invasive ventilation.
On April 15-17, 2021, more than 80 experts from disease control, medical care, universities and scientific research institutes focused on the challenges and opportunities faced by infectious disease prevention and control and biosafety in China, focused on key issues such as big data and monitoring network, detection and traceability technology, drug resistance control and vaccine research and development strategies, and reached a consensus: (1) In view of the current situation of infectious disease prevention and control and the need to ensure biosafety in China, it is urgent to establish a cross-departmental and all-round microbiological scientific database and laboratory monitoring network; (2) Pathogen screening, identification and typing traceability technology needs to develop in the direction of ultra-sensitivity, intelligence and networking, and the standards and application scope of pathogen identification and traceability technology based on high-throughput sequencing should be standardized; (3) It is urgent to establish a cross-departmental drug resistance monitoring system to strengthen the monitoring of cross-species transmission of drug-resistant bacteria; (4) Apply scientific theories and new technologies to guide and improve future vaccine emergency research and development and vaccination strategies. Make expert advice based on the above questions.
To analyze the epidemiological, clinicopathological and prognostic characteristics of clear cell papillary renal cell carcinoma (CCPRCC) based on Chinese patient population.
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.
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).
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.
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.
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.
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 (allP<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).
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.
To explore the safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy in the treatment of renal tumors.
The 65 patients with renal tumors undergoing laparoscopic microwave ablation combined with partial nephrectomy from November 2017 to May 2021 were retrospectively analyzed. There were 46 males and 19 females. The average age was (56.6±14.1) years. The mean body mass index was (25.7±3.3) kg/m2. The tumors located in the left kidney in 30 cases and the right kidney in 35 cases. The ECOG score was 0 in 59 patients and 1 in 6 patients. The mean maximum diameter of the tumors was (2.3±1.0) cm(1.0-5.0 cm). According to R.E.N.A.L. scoring, 41 cases were of low difficulty (4-6 points), 23 cases of medium difficulty (7-9 points) and 1 case of high difficulty (10-12 points). The renal tumors were ablated by laparoscopic microwave ablation, then followed by partial nephrectomy. Postoperative complications were observed and the prognosis was assessed by CT or MRI.
The mean duration of operation was (76.6±19.4) min (40-120 min). The median intraoperative blood loss was 20 ml(5-50 ml). The median duration of postoperative hospitalization was 4 d(3-6 d). Complications of Clavien grade Ⅰ were found in 11 patients (fever, nausea and vomiting, lumbar pain), and no complications were grade Ⅱ or above. Postoperative pathology showed that no positive margin was found, and 46 cases of clear cell renal cell carcinoma (AJCC stage: T1a stage 42 cases, T1b stage 4 cases; WHO/ISUP classification: 21 cases of grade 1, 23 cases of grade 2, 2 cases of grade 3); 2 cases of type 1 papillary renal cell carcinoma (stage T1a, grade 1); 1 case of type 2 papillary renal cell carcinoma (T1b stage, grade 2); 2 cases of renal chromophobe carcinoma (all stage T1a); 1 case of low-grade malignant potential multilocular cystic renal tumor; 2 cases of adenocarcinoma (combined with the postoperative history of rectal cancer, metastasis was considered); 6 cases of renal angiomyolipoma; 2 cases of eosinophiloma; 1 case of papillary adenoma; 1 case of benign renal cyst and 1 case of renal hemangioma with calcification. The median follow-up was 24 months (1-42 months). Sixty-three patients survived and two died (one due to heart disease and one due to metastatic colorectal cancer). According to postoperative imaging, there were no signs of tumor recurrence or metastasis in other cases. Blood tests were performed regularly, and no significant abnormalities occurred.
The safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy for the treatment of renal tumor is satisfactory, such as less intraoperative bleeding, fewer complications, less effect on renal function and postoperative pathology, providing a potential option for renal tumor treatment.
To compare the effects of ice water kidney cooling and traditional non-cooling surgery on postoperative renal function in robot-assisted laparoscopic partial nephrectomy, and explore its clinical value in protecting renal function.
A retrospective analysis is conducted on the base of the clinical data of patients undergoing robot-assisted laparoscopic partial nephrectomy in Second Affiliated Hospital of Navy Military Medical University from January to November 2019. A total of 89 cases, of which 21 cases were treated with ice water to cool the kidney surface and block the renal artery during the operation (cooling group); 68 cases only clamp the renal artery (control group). Compare the difference of the operation time, R.E.N.A.L. score, intraoperative blood loss, renal artery block of time,postoperative intestinal recovery time, cut edge positive rate, preoperative and postoperative blood electrolyte levels, the change of blood creatinine and GFR before operation and the first and third months after the operation and other indicators between two groups.
All the 89 patients completed the operation normally, and no conversion to open surgery or to general endoscopic surgery. The two groups of patients had statistically significant differences in tumor diameter [7.0(5.5, 8.0) vs 3.8(3.0, 5.0) cm, P<0.001], R.E.N.A.L. score [8.0(6.5, 8.0) vs 6.0(5.0, 8.0),P=0.003], Chloride (Cl-) in the blood [(103.29±2.81) vs (104.74±2.58) mmol/L, P=0.030], (P<0.05) in the preoperative data. There were significant differences in renal artery occlusion time [20.0(18.5, 27.5) vs 19.0(15.0, 21.0) min,P=0.023] and operation time [168.0(130.0, 182.5) vs 130.0(110.0, 177.5) min, P=0.007] between the two groups (P<0.05). There was no significant difference in the blood creatinine after one or 3 month as well as for the glomerular filtration rate (allP>0.05). After follow-up for 3-24 months, no tumor recurrence or distant metastasis occurred in both groups, and no related complications caused by ice-free Water Cooling Technique in the cooling group.
It is safe and effective to apply kidney surface cooling technique with ice water in robot-assisted laparoscopic partial nephrectomy for complex kidney tumor. It can significantly reduce the renal parenchyma warm ischemia injury of renal parenchyma. And it′s conducive to the recovery of patients with postoperative renal function, which can maximize the protection of renal function of patients.
To investigate the relationship between tumor angiogenesis and renal cancer stem cells.
The primary cell culture method was used to extract and isolate RCSCs, and then qRT-PCR and Western blot methods were used to detect the expression levels of the kidney cancer stem cell markers CD105 and Sox2 genes and proteins from different MVD kidney cancer tissues. Using TCGA database, analyze the correlation between tumor angiogenesis markers and tumor stem cell regulatory genes.
The stem cell markers CD105 and Sox2 genes in RCSCs derived from high MVD kidney cancer tissues were respectively increased by (2.34±1.77) times and (3.92±1.41) times (PCD105<0.01, PSox2<0.05)and protein levels were increased by (5.12±3.31) times and (4.90±3.30) times(PCD105<0.05, PSox2<0.01).Meanwhile,up to 30% of stem cell promoting stemness regulatory genes are positively correlated with angiogenesis genes CD31/PECAM1 and KDR, and 64 genes are also strongly positively correlated with CD31/PECAM1 and KDR genes.
The high microvessel density of kidney cancer is strongly correlated with the existence of renal carcinoma stem cells.
To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis.
Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs.
Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated.
DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.
To explore the role of diaphragm ultrasound in guiding the successful weaning of ventilators in patients undergoing heart valve replacement.
Prospectively selected 103 patients who received heart valve replacement in the Department of Cardiac Surgery, Fuwai Hospital of the Chinese Academy of Medical Sciences from December 2019 to February 2021 were selected, who have received mechanical ventilation for ≥48 h and have entered the pre-weaning spontaneous breathing test. The patients were divided into a successful weaning group (n=83) and failed weaning group (n=20) according to the patient′s weaning result. Receiver operating characteristic (ROC) curve was used to evaluate the value of diaphragm thickening rate and diaphragmatic excursion to predict the result of ventilator weaning.
Among 83 patients in the successful weaning group, 52 were male patients and 31 were female patients, with an average age of (56.5±5.5) years; 20 patients in the failed weaning group included 12 male patients and 8 female patients, with an average The age is (57.3±6.2) years old.The left DTF, right DTF, left DE, and right DE of the patients in the successfully weaned group were (39.0±17.8)%, (57.7±1.2)%, (11.9±4.3) mm, (18.5±1.4) mm, respectively, which were higher than those in the weaning failure group (18.1±4.5)%, (19.9±2.3)%, (6.2±2.8) mm, (11.9±1.5) mm, respectively. And the differences were statistically significant (all P<0.05). ROC curve analysis showed that the best cut-off values, the sensitivity and the specificity for the thickening rate of the left diaphragms of patients with successful weaning were 61%, 90.46% and 87.83%, respectively; while the best cut-off values, the sensitivity and the specificity for the thickening rate of the right diaphragms of patients with successful weaning were 88%, 96.07% and 89.67%, respectively. The optimal cut-off values, the sensitivity and the specificity of mobility of the left right diaphragms of patients are 11.3 mm, 81.38% and 80.24%, respectively; while the optimal cut-off values, the sensitivity and the specificity of right diaphragms of patients were 12.7 mm, 87.23% and 85.56%, respectively.
Diaphragm ultrasound can more accurately predict the outcome of ventilator weaning in patients undergoing heart valve replacement surgery, and it has good clinical application value.
To construct the gene modified probiotic Escherichia coli nissle1917 (EcN) which can express human Elafin protein and to explore its protective effect on the acute colitis in mice.
The recombinant plasmid with human Elafin gene was constructed and then transferred to EcN. Western blot results confirmed that the engineered probiotic expressed Elafin successfully in vitro. C57/BL6J mouse was used in this study and were randomly divided into 4 groups according to different treatment: PBS gavage (PBS group); DSS administrated (DSS group); DSS administrated with wild-type EcN (EcN-WT) gavage (EcN-WT group); DSS administrated with EcN-Elafin gavage (EcN-Elafin group). Body weight and disease activity index (DAI) were measured every day. The length of mice colons in each group were measured after euthanasia. The degree of inflammation of intestinal mucosa in each group was measured through histopathological scoring. The proportion of neutrophils and macrophages infiltrated into colon lamina propria was detected by flow cytometry. The protein expression levels of pro-inflammatory cytokines TNF-α, IL-6 and chemokine CXCL-1 in colonic tissue were quantified by enzyme-linked immunosorbent assay.
Elafin protein could be detected in the supernatant of EcN-Elafin culture medium and EcN-Elafin homogenates. Compared with DSS group, the weight loss and DAI score of EcN-Elafin group and EcN-WT group were both significantly improved. The colon length of EcN-Elafin group was significantly longer than that of DSS group. The histological score of colitis in EcN-Elafin group was significantly lower than that in DSS group (5.3±2.3 vs 9.3±1.4, P<0.05). In EcN-Elafin group, the proportion of neutrophils[(8.65±1.49)% vs (17.60±2.16)%,P<0.01]and macrophages[(3.79±0.26)% vs (5.73±0.45)%,P<0.01]infiltrated into the colon lamina propria was significantly decreased compared with DSS group. The protein expression levels of TNF-α, IL-6 and CXCL-1 in EcN-Elafin group and EcN-WT group were significantly lower than those in DSS group.
Elafin-expressing EcN can protect against DSS-induced acute colitis in mice and may have provided an effective and cost-efficient method for the treatment of IBD.
To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.
To investigate the application of totally visceral sac separation (TVS) in the treatment of ventral hernia, to summarize the operation procedure and to analyze its safety and effectiveness. Twenty-one consecutive primary and secondary ventral hernias cases were repaired using the TVS procedure from December 2019 to December 2020. A large mesh should be placed in retrorectus sublay or underlay preperitoneal using the minimally invasive procedure. The indications for this procedure include umbilical, incisional hernia, linea alba hernia, lumbar hernia, and parastomal hernia. All the operations were successful, of which 2 cases were converted to laparotomy because of the failure of anterior peritoneal cavity construction and the difficulty of anterior defect closure. The mean operation time was 140 mins (70-260 min), postoperative pain was mild, and the mean visual analogue scale(VAS) was 2.5 (1-4) on the first postoperative day. There were no recurrent cases during the follow-up for more than 6 months. TVS procedure is safe and highly reproducible. Without expensive anti-adhesion mesh and fixation tacker, the technology of TVS is a good technique for the surgical treatment of ventral hernia.
Malignant tumors have increasingly become the main diseases affecting human health. After patients receive comprehensive treatment such as surgery, radiotherapy and drugs, they are generally discharged as soon as possible and followed up at home. During the home observation period, due to the lack of close and timely communication with medical staff, treatment-related adverse reactions are often not discovered and dealt with in time, which will cause harm to the patient's body. Patient Report Results (PRO) is a new model of out-of-hospital patient follow-up management with doctor-patient interaction that has emerged in recent years. There have been many related research reports abroad. This article will provide a comprehensive introduction to PRO in this regard and explore the Chinese model of PRO management of out-of-hospital oncology patients.
McCune-Albright syndrome is a rare disease involving multiple organs, and its pathogenesis is related to mutations in the gene of guanine nucleotide binding protein alpha subunit encoded by the GNAS gene. This syndrome mainly causes three typical manifestations: endocrine abnormalities (including precocious puberty, hyperthyroidism, Cushing syndrome, etc.), multiple bone fibrous dysplasia, and skin milk caffeine spots. In addition, it has effects on digestive system and blood system. This article reviews the pathogenesis, clinical manifestations and the latest progress in diagnosis and treatment, in order to provide new ideas for clinical diagnosis and treatment and long-term management.
Renal cell carcinoma (RCC) is a common fatal malignancy that accounts for more than 2% of all adult cancers, and 80% of renal cell carcinomas are subdivided into clear cell renal cell carcinoma (ccRCC) based on histological and cytogenetic characteristics. Perirenal adipose tissue (PAT) is a type of white adipose tissue (WAT) located between the renal fascia and the renal capsule. During tumorigenesis, ccRCC cells can penetrate the renal capsule and enter the PAT, which is associated with poor prognosis of renal cancer. However, the interaction between ccRCC and PAT has not been well investigated. Through in-depth exploration of the two-way communication between ccRCC cells and PAT, the researchers found that ccRCC cells secrete parathyroid hormone-related protein (PTHrP) through paracrine mode to activate the PKA pathway to drive the browning of adjacent PAT, which enhances the metabolism of brown perirenal adipocytes and releases a large number of metabolites, in which excess lactic acid is released into the tumor microenvironment, thus promoting the growth, invasion and metastasis of ccRCC, constituting a new possible mechanism to promote the growth of ccRCC tumors. This study suggests that removal of adjacent adipose tissue during kidney cancer surgery may prevent the flow of metabolites of brown adipocytes, thus improving the prognosis after surgery.
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