[Prevalence of frailty and associated factors among kidney transplant recipients].

Objective: To investigate the prevalence of frailty among kidney transplant recipients and to analyze the influential factors of frailty after kidney transplantation. Methods: We retrospectively included 201 kidney transplant recipients who were followed up in the Department of Urology, Beijing Chao-yang Hospital, Capital Medical University from November 2020 to May 2022. We investigated the prevalence of frailty based on the Fried Frailty Scale (including unexpected shrinking, slow walking speed, poor grip strength, low physical activity, and exhaustion). Then the logistic regression model and CART decision tree model were established separately to explore the influential factors of frailty after kidney transplantation. Results: Frail kidney transplant recipients accounted for 25.9% (n=52) of all participants. The age [M (Q1, Q3)] of the frailty group was higher than that of the non-frailty group, and the median ages of the two groups were 57(49, 62) and 46(38, 56) (P<0.001); the males accounted for 51.9% (n=27) and 62.4% (n=93), respectively. There was no significant difference in gender composition (P=0.244). Among the five components of Fried Frailty Scale, the incidence of unexpected shrinking was the lowest (19.4%, 39/201). In the frailty group, the frailty combination with the highest incidence was slow walking speed+low physical activity+exhaustion, which was 19.2% (10/52). The logistic regression model showed that advanced age (OR=1.062, 95%CI: 1.005-1.123), history of acute rejection (OR=16.776, 95%CI: 2.288-123.028), increased neutrophil/lymphocyte ratio (NLR) (OR=2.096, 95%CI: 1.158-3.792), and comorbidity (OR=10.600, 95%CI: 1.828-61.482) were risk factors for frailty among kidney transplant recipients, and high serum albumin level (OR=0.623, 95%CI: 0.488-0.795) was a protective factor. The CART decision tree grew in three layers with four terminal nodes, and three explanatory variables were screened out: serum albumin, NLR, and age. The accuracy, sensitivity, and specificity of the logistic regression model were 87.1% (95%CI: 82.5%-91.7%), 69.2% (95%CI: 54.7%-80.9%), and 93.3% (95%CI: 87.7%-96.6%), respectively. The area under the ROC curve (AUC) of the logistic regression model was 0.951 (95%CI: 0.923-0.978). The accuracy, sensitivity, and specificity of the CART decision tree model were 91.0% (95%CI: 87.0%-95.0%), 82.7% (95%CI: 69.2%-91.3%), and 94.0% (95%CI: 88.5%-97.0%), respectively. The AUC of the CART decision tree model was 0.883 (95%CI: 0.819-0.948). Conclusions: The prevalence of frailty among kidney transplant recipients in this study is 25.9%. Advanced age, history of acute rejection, low serum albumin level, increased NLR, and comorbidity are likely to be associated with the long-term frailty among kidney transplant recipients.

[Establishment and analysis of prediction model for invasive subsolid pulmonary nodules based on radiomics].

Objective: To evaluate the best radiomic features based prediction model for identifying the histopathological subtypes of invasive adenocarcinoma or noninvasive pulmonary nodules appearing as subsolid nodules. Methods: A total of 352 patients (108 males and 244 females, median age was [M(Q1,Q3)]57 (50,65), underwent high-resolution chest CT and appearing as subsolid nodules and further treated by surgical resection whose subsequently pathological results were classified as atypical adenomatous hyperplasia (AAH), carcinoma in situ (AIS), microinvasive carcinoma (MIA), invasive adenocarcinoma (IA), from January 2015 to September 2019, in Radiology Department of Zhongda Hospital Affiliated to Southeast University and Jinling Hospital, Medical School of Nanjing University were retrospectively collected. They were divided into non-invasive group (n=233) and invasive group (n=119) according to pathological findings. According to the ratio of training set: internal test set: external test set, which is about 3∶1∶1,the patients in Zhongda Hospital Affiliated to Southeast University were randomly divided into training set (n=215, non-IA∶IA 155∶60) and internal test set(n=69, non-IA∶IA 52∶17), meanwhile a certain number of patients in Jinling Hospital, Medical School of Nanjing University(n=68, non-IA∶IA 26∶42)were randomly selected as an independent external test set. Particular quantitative parameters of the nodules, radiomic features, morphological characteristics, clinical data, and serum tumor markers were recorded. Radiomic label was constructed using LASSO regression method. The morphological model, CT model and comprehensive model were constructed by binary logistic regression and were verified in test sets, respectively. Results: Shape_MinorAxis(Gradient),Glszm_ZoneEntropy(LBP) were selected as the two most significant features based on training set. Radiomic tag=1.065 75×Shape_MinorAxis(Gradient)+0.030 58×Glszm_ZoneEntropy(LBP). Comparing the prediction performance of all models in each data cohort, the CT model (Ln(P/1-P)=-2.417 11+1.031 60×Radimic tag+1.203 06×Diameter+1.614 21×(Pleural indentation sign = Y) constructed by radiomic label, pleural depression, and quantitative parameters (diameter, average density) was much better than other models and was chosen as the optimal model, with an AUC of CT models in training cohort and test cohort was 0.954 (95%CI: 0.927-0.981), 0.865 (95%CI:0.764-0.966), better than morphological model 0.857 (95%CI:0.796-0.918), 0.818(95%CI: 0.686-0.949) and comprehensive model 0.951(95%CI: 0.921-0.981), 0.856(95%CI: 0.730-0.982), respectively. Conclusion: The integrative CT model has a better prediction efficiency for identifying invasive or noninvasive nodules appearing as subsolid nodules.

CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair.

BACKGROUND: Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear. PATIENTS AND METHODS: To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss. RESULTS: We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair. CONCLUSIONS: Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.

Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of gamma-ray and the involvement of low dose radiation inducible CHD6 gene in cell proliferation and radiosensitivity.

PURPOSE: To identify candidate genes specifically involved in response to low-dose irradiation in human lymphoblastoid cells; to better clarify the role of the human chromodomain helicase DNA binding protein 6 gene (CHD6), one of these genes, in cell proliferation and radiosensitivity. MATERIALS AND METHODS: DNA microarray technology was used to analyse global transcriptional profile in human lymphoblastoid AHH-1 cells at 4 h after exposure to 0.5 Gy of gamma-ray. Gene expression changes were confirmed by semi-quantitative reverse transcription--polymerase chain reaction (RT-PCR) and Northern blot. RNA interfering technology was employed to knock-down the CHD6 gene in A549 cells. Colony-forming ability was used to analyse radiosensitivity. RESULTS: The microarray assay revealed a set of 0.5 Gy-responsive genes, including 30 up-regulated genes and 45 down-regulated genes. The up-regulated genes include a number of genes involved in: signal transduction pathways, e.g., STAT3, CAMKK2, SIRT1, CREM, MAPK3K7IP2 and GPR56; transcription or DNA-binding, e.g., CHD6, CRSP3, SNURF, SH2 domain binding protein 1 and MIZF. Some of the down-regulated genes are involved in: cytoskeleton and cell movement (WASF2, LCP1, MSN, NIPSNAP1, KIF2C); DNA replication and repair (MCM2, MCM3, MCM7 and XRCC-4). Radiation-increased expression of CHD6 was also found in A549 cells and HeLa cells. The sustained CHD6 induction was restricted to relatively low doses (0.2 Gy or 0.5 Gy), no change occurring after 4 Gy irradiation. Silencing of CHD6 mediated by siRNA increased the growth rate of A549 cells by 40 approximately 60%. Most importantly, silencing CHD6 led to an increased radioresistance of A459 cells to radiation doses up to 2 Gy, but barely affected the sensitivity of cells at 4 and 8 Gy. CONCLUSION: This study has identified a set of genes responsive to 0.5 Gy of gamma-rays. CDH6 gene can be specifically up-regulated by low dose irradiation, and its inducible expression could be involved in a low dose hypersensitive response.

[Studies on the anthraquinones of Cassia siamea].

AIM: To study the anthraquinone constituents of the stem of Cassia siamea. METHODS: The compounds were isolated by chromatography on silica gel, MHPLC, and identified on the basis of spectral analysis including IR, EI-MS, FAB-MS, 1HNMR, 13CNMR and DEPT. RESULTS: Three compounds were isolated and identified as: chrysophanol (I), chrysophanol-1-O-beta-D-glucopyranoside (II) and 1-[(beta-D-glucopyranosyl-(1-->6)-0-beta-D-glucopyranosyl) oxy]-8-hydroxyl-3-methy-9,10-anthraquinone (III). CONCLUSION: III is a new compound, II was obtained from this plant for the first time.

[Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index].

OBJECTIVE: To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas. METHODS: The expression of P21, P53, MDM2, and proliferative cell nuclear antigen (PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples. As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at -70 degrees C were investigated. In immunohistochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtain labeling index (LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients. In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells. RESULTS: In p21 mRNA in situ hybridization, the positive staining was present in 87.5%. In immunohistochemistry, positive P21, P53, MDM2, and PCNA staining were presented in 75.6%, 68.3%, 65.9%, 100% respectively. Higher levels of P21 protein expression were seen in higher histological grade (P = 0.001). The association between P21 expression positively correlated with proliferation index. But not with P53 expression and MDM2 expression. The association between P53 expression and proliferation indices were statistically significant, but the expression of P53 was not related to tumor grade. There was no association between MDM2 expression and grade, or cellular proliferation index. Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI (P = 0.000) and P21 LI (P = 0.001). CONCLUSIONS: (1) Both p21 mRNA and P21 protein were overexpressed in human astrocytomas, the overexpression was related to cellular proliferation index, but was not related to P53 expression, suggesting there could be P53-independent pathway to induce the P21 expression, in addition, the overexpression of P21 alone appeared insufficient to suppress tumor growth, provided the participation of PCNA. (2) The expression of P53 protein was associated with proliferation indices, but was not with the tumor malignancy, this indicated that the inactivation of P53 might be the early event in the growth of human astrocytomas. (3) P21 labeling index and cellular proliferation index influenced the tumor histological grade, our data indicated that p21 gene might play a role in the progression of human astrocytomas.

[Studies on the chemical constituents of Uncaria yunanensis Hsia. C.C].

AIM: To research the chemical constituents from dried roots of Uncaria yunanensis Hsia. C. C. METHODS: Modern chromatography was used to isolate chemical components. Their structure were identified by spectral analysis. RESULTS: Seven compounds were isolated and identified as 3 beta, 6 beta, 19 alpha-trihydroxyurs-12-en-28 oic acid (I), 23-nor-24-esomethylene-3 beta, 6 beta-19 alpha-trihydroxyurs-12-en-28 oic acid (II), 3-oxo-6 beta, 19 alpha-dihydroxyurs-12-en-28 oic acid (III), oleanic acid (IV), 5,7,3',4'-tetrahydroxy-flavan-3-ol (V), beta-yohimbine (VI) and diangoutengjian I (VII). CONCLUSION: All of the above compounds were isolated for the first time from the root of this plant. Among them, compound VII is a new one.

[Selective ventral rhizotomy for the treatment of spastic cerebral palsy].

OBJECTIVE: To understand the influence of selective ventral rhizotomy on the function of lower extremity and to investigate its effect in the treatment of spastic cerebral palsy. METHODS: Ten domestic dogs were used in this study. Under anesthesia, the lumbar spinal canal was reached through posterior approach. The ventral rami consisted of left L5, L6 and L7 spinal nerves was separated. The electromyographic changes of each branch of the rami was examined by electrical stimulation. 60 percents of the L6 ventral nerve root which was the major innervation of the gastrocnemius muscle in dogs, and 30 percents of the other two rami were culted off. The muscle tone, the coordinated movement and balanced capacity of the dogs were observed. After one month, the electrophysiological changes of the biceps femoris, semitendinous, gastrocnemius and anterior tibial muscles were examined and compared with that of the identical muscles of the contralateral limbs. RESULTS: Selective ventral rhizotomy was well correspondent to the innervated muscles. After operation, the coordinated movement and balanced capacity were good, but the muscle tone of the corresponding muscle was lowered. This technique was applied on 3 patients with satisfactory short-term results. CONCLUSION: For the treatment of spastic cerebral palsy, it is worth trying the selective ventral rhizotomy.

Echocardiography of the right ventricle-to-pulmonary artery homograft conduit of patients with transposition of the great arteries or double outlet right ventricle undergoing the Rastelli procedure.

BACKGROUND: Aortic valved homograft conduits have been valuable in right ventricular outflow tract (RVOT) reconstruction in complex congenital heart disease. METHODS: Since 1995, 12 patients ranging in age from 3 to 22 years, with transposition of the great arteries or double outlet right ventricle associated with pulmonary stenosis and ventricular septal defect, underwent the Rastelli procedure with the RVOT reconstruction utilizing cryopreserved aortic valved homograft conduits. RESULTS: Operative deaths for three patients were caused by the complexity of the heart defects (25%). One late death (8.33%) occurred as a result of pulmonary embolism one month after conduit implantation. The remaining eight patients (66.67%) survived asymptomatically with a mean postoperative hospitalization of 22 days. Preoperative Doppler echocardiographic flow visualization distinguished not only the corresponding location among the atrium, ventricle and great arteries, but also intracardiac. Mosaic flow pattern could be detected in the right ventricle and right atrium (n = 11). Postoperative echocardiographic flow visualization showed the valved homograft extracardiac conduit lay between the right ventricle and the pulmonary artery, and the valve inside the conduit could faintly be seen. Mosaic flow pattern could be observed with the systole and diastole jet in the cardiac circle (n = 8). Peak velocity and pressure gradient across the pulmonary valve after the Rastelli procedure were significantly decreased when compared with those before operation (4.13 +/- 0.44 m/s vs. 3.15 +/- 1.13 m/s, p = 0.032; 72.46 +/- 15.79 mmHg vs. 39.87 +/- 23.23 mmHg, p = 0.003). However, there were no significant differences between pre- and postoperative peak velocity and pressure gradient beyond the pulmonary valve. CONCLUSIONS: Apart from operative mortality, the application of aortic valved homograft conduits were all excellent choice for the correction of complex congenital heart disease.

[Primary pericardial mesothelioma: a clinicopathological analysis of 7 cases].

Primary pericardial mesotheliona is a clinical rarity. 7 cases were reported in this paper. There were no typical clinical symptoms and signs. It could not be diagnosed simply with chest film, ECG or echocardiagram and was usually misdiagnosed as constritive pericarditis, tuberculous pericarditis etc. In order to make correct diagnosis, some investigative diagnose methods such as pathological examination of pericardial fluid and pericardial biopsy, Gallium-67 scintigraphy, Ber-EP4 antibody and immunohistochemical procedures should be employed.

[Immunohistochemical quantitative study of glial fibrillary acid protein and vimentin of astrocytomas].

Two different types of intermediate filaments, vimentin (VIM) and glial fibrillary acidic protein (GFAP) were studied by immunohistochemical quantitative analysis using image analyser in 25 cases of astrocytomas, grade II to IV. The results showed that the VIM and GFAP distribution patterns were similar in all cases of astrocytomas, but the expression of VIM in poorly differentiated astrocytoma (grade III and IV) being more frequent and intense than in well differentiated astrocytomas (grade II), the expression of GFAP in well differentiated astrocytomas (grade II) is more frequent and intense than in poorly differentiated astrocytomas (grade III and IV). We suggest that there is a negative relation between the reaction of GFAP and the degree of malignancy in astrocytomas and a positive correlation between reaction of VIM and the degree of malignancy in astrocytomas.

[Pathology and immunohistochemical demonstration of beta-HCG in intracranial primary germinoma].

Clinical pathologic observation and immunohistochemical demonstration on beta--HCG are reported in 13 cases of intracranial primary germinomas, including 7 cases of germinomas in the region of the pineal gland and 6 cases in the hypothalamic area. Among them, there were 11 cases of simple type and 2 cases of beta--HCG--producing tumors with a character of differentiation of trophoblasts in the latter. This paper supports the concept that intracranial primary germinoma is an atypical teratoma arising from the germ cells. The significance of beta--HCG immunohistochemical demonstration in the pathologic diagnosis of germinomas and the mechanism of endocrine disturbance are discussed.

[Effects of cholecystokinin, gastrin and proglumide on bile secretion in rats].

The aim of this study is to observe the effects of pentagastrin (P-Gas), CCK-8 and proglumide (PGM), which were used solely or in combination on choleresis in rats prepared with neck vein and hepatic-bile duct intubation. The results indicate that: 1) P-Gas does not provide cholecystic effect; 2) CCK-8 has a little stimulating effect on bile flow and output of bicarbonate; 3) PGM increases the bile flow and the outputs of biliary bicarbonate and chloride significantly, but it can not increase the bile acid output; 4) after administration of CCK-8 2.3 micrograms/(kg.h) iv infusion and PGM 200 mg ig in combination the outputs of bile flow, bicarbonates and chloride were greater than to PGM given alone, but after P-Gas 2 micrograms/(kg.h) was used together with PGM the outputs were less than to PGM given alone. The results suggest that PGM has a remarkable effect of choleresis and its mechanism may be attributed to bile acid independent fraction, while CCK-8 was only a weaker stimulant and P-Gas can not modify the bile flow and bile components. In addition, there may be a synergism effect between PGM and CCK-8 and an antagonist suppression between PGM and P-Gas on choleresis in the rat.

[Effect of proglumide on choleresis in rats].

We are the first to report that proglumide (PGM) has a marked effect on promoting choleresis in rats. After iv infusion PGM 50, 100, 200, 400 mg/(kg.h), the bile quantities of 120-150 min were 0.4 +/- 0.14, 0.46 +/- 0.11, 0.75 +/- 0.25, 0.87 +/- 0.21 ml/30 min, respectively. They were significantly higher values than either basic bile flow (0.24 +/- 0.06 ml/30 min) or the solvent control of 5% NaHCO3 (0.22 +/- 0.13 ml/30 min, P less than 0.01) and obviously dose-dependent. After ig PGM 200 mg, bile flow observed at the peak of secretion between 60-90 min was 0.67 +/- 0.22 ml/30 min. Compared to that observed before PGM administration, the bile fluid collected was found to have increased 1.7-3.2 times, up to even 7 times. The choleretic effect continued 8-12 h after the infusion was terminated. The secretions of HCO3- and chlorides in the bile also increased during PGM infusion as compared with the control (P less than 0.05-0.01). On the contrary, the concentrations of cholic acids decreased remarkably (P less than 0.05-0.01). It is suggested that the mechanism of choleresis promoted by the infusion of PGM may be cholic acid-independent, but that it is related to the secretion of inorganic salts in cholangiole. Compared with three other choleretics commonly used clinically, phenylpropanol, dehydrocholic acid and sodium taurocholate, the effect of PGM is significantly superior (P less than 0.01).

[Pathological analysis of 1458 cases of tumor in the sella turcica region].

The sella turcica region is an anatomical site preferential for various types of intracranial tumors. Pathological analysis of 1458 cases of tumor in this region is presented. They comprised 20.16% of the intracranial tumors. Among them, 846(59.1%) were pituitary adenomas, 433(29.7%) craniopharyngiomas, 91(6.2%) meningiomas and 42(2.9%) germinomas. In pituitary adenomas, chromophobe adenoma was predominant, mixed cell adenoma next and no basophilic adenoma was observed. Of craniopharyngiomas they were divided into cystic, partly solid and cystic, and calcified types grossly and histologically into adamantinomatous, squamous and calcified types. In this kind of tumor, well differentiated cells were consistent to the clinical benign course. For meningiomas, histologically meningotheliomatous type was most common in this region. In previous reports, germinomas in the sella turcica region were so-called ectopic pinealoma. Now it is well known that this tumor arises from germ cells, hence, the synonym "ectopic pinealoma" is obsolete. The germinomas in the sella turcica region accounted for 44.68% of all intracranial germinomas. Microscopic picture of this tumor was similar to those of seminoma of the testicle and dysgerminoma of the ovary. Although gliomas, teratomas, giant cell tumors and chondromas were uncommon in the sella turcica region, the authors believe that they should be considered in the differential diagnosis of tumors in the sella turcica region.