Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels / 中华儿科杂志

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Mechanism of rhein inhibition of colorectal cancer through arginine metabolism based on protein chip / 药学学报

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

Behavioral-electrophysiological observation of the involvement of dopamine D1 receptor of the rat anterior cingulate cortex in the regulation of pain-related emotion / 生理学报

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment / 生理学报

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O

Therapeutic effect of gene silencing peptidyl arginine deaminase 4 on pulmonary interstitial lesions induced by collagen-induced arthritis mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the therapeutic effect of gene silencing peptidyl arginine deaminase 4 (PAD4) on pulmonary interstitial lesions induced by collagen-induced arthritis (CIA) mice, and possible mechanisms.@*METHODS@#A CIA mouse model was established in DBA/1 mice, followed by a tail vein injection of the virus solution prepared by the PAD4-siRNA expression vector once a week for 8 times. The mice were sacrificed at the end of the experiment. The expression of PAD4 mRNA in lungs was detected by real-time quantitative PCR (qRT-PCR). The expression of PAD4 protein was detected by tissue immunohistochemistry. Cell culture was performed by spleen tissue. Flow cytometry changes in the ratio of Tfh cells to Tfr cells were examined; lung staining was performed in the lungs to observe changes in lung pathology.@*RESULTS@#(1) Compared with the blank group, the expression of PAD4 mRNA in the lung tissue of the model group increased, the difference was statistically significant (P < 0.05). PAD4 mRNA in the lung tissue of the CIA mice after PAD4-siRNA treatment. The expression level was significantly lower than that of the model group and the negative control group, and the difference was statistically significant (P < 0.05). (2) Red fluorescence was less in the lung tissue of the blank group, while more red fluorescence was observed in the inflammatory cell infiltration area and trachea around the lung tissue of the model group and the negative control group, and the red fluorescence of the three groups after PAD4-siRNA treatment was significantly reduced; (3) Compared with the blank group, the proportion of Tfh cells in the model group increased, the difference was statistically significant (P < 0.05), the proportion of Tfh cells in spleen cells of the CIA mice after PAD4-siRNA treatment was significantly lower than that of the model group and the negative control group, the difference was statistically significant (P < 0.05); compared with the blank group, in the mouse spleen cells in the model group the proportion of Tfr cells was slightly decreased, but the difference was not statistically signifi-cant. The proportion of Tfr cells in the spleen cells of the mice increased after PAD4-siRNA treatment, but the difference was statistically significant only in the PAD4-siRNA2 group compared with the model group and the negative control group (P < 0.05); (4) The proportion of Tfh/Tfr in the spleen cells of the model group was increased, compared with the blank group, the difference was statistically significant (P < 0.05); the ratio of Tfh/Tfr in the three groups after PAD4-siRNA treatment all decreased, the difference was statistically significant (P < 0.05); (5) Compared with the blank group, the alveolar wall of the lung tissue of the model group was thickened, the inflammatory cell infiltration was increased, and the lung tissue destruction and inflammatory infiltration of the CIA mice were decreased after PAD4-siRNA treatment. The degree of reduction was reduced.@*CONCLUSION@#Gene silencing of PAD4 can reduce the proportion of Tfh cells, increase the proportion of Tfr cells, reverse the proportion of Tfh/Tfr, and reduce the degree of interstitial lesions and inflammatory infiltration of lung tissue.

Clinical value of D-dimer and CRP in evaluating the prognosis of 2019 novel coronavirus-infected pneumonia / 医学研究生学报

ObjectiveTo investigate the relationship between the levels of D-dimer and inflammatory factors C-reactive protein（CRP）and prognosis in patients with 2019 novel coronavirus-infected pneumonia（COVID-19）.Methods The clinical data of a total of 242 patients with COVID-19 who were treated in hospital from February 4th 2020 to February 18th 2020 were analyzed retrospectively. According to the classification standard,the patients with COVID-19 were divided into common patients(131 cases), severe patients（88 cases）, and critical patients（23 cases）. The difference between the levels of D-dimer and CRP in patients with pneumonia of different severity and clinical outcomes was compared and the correlation between D-dimer and CRP was analyzed.ResultsThe levels of D-dimer and CRP in severe and critical patients were significantly higher than those in common patients(P<0.05). The levels of CRP in critical patients were significantly higher than those in severe patients(P<0.05). These two indicator levels of patients who died of COVID-19 within 30 dayswere significantly higher than those who survived. Pearson correlation analysis showed that the levels of D-dimer were positively correlated with the levels of CRP(r=0.649，P<0.05).ConclusionD-dimer and CRP are highly expressed in severe and critical patients, and the severe abnormality of the two indicators in the early stage of COVID-19 predicted the poor prognosis. D-dimer and CRP have certain clinical value in evaluating the severity and prognosis of COVID-19.

Expression and Clinical Prognostical Significance of RIP2 in Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression and prognosis significance of receptor interacting protein 2 (RIP2) in diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>The expression of RIP2 in DLBCL GCB and non-GCB type was detected by immunohistochemistry, at same time the expressions of BCL-2 and C-MYC were detected. Then, the role of RIP2 in development of DLBCL was analyzed by related clinical and pathological parameters.</p><p><b>RESULTS</b>The expression of RIP2 was related with middle-high risk group by IPI score, the An Arbor stage III+IV and intranodal lesions, and the differences were statistically significant (P<0.05). Besides, the single factor survival analysis suggested that GCB-type DLBCL showed a higher survival rate than that in non-GCB type(P<0.05). Patients with RIP2showed a lower survival rate as compared with patients with PIP2(P<0.05), among which the patients receiving R-CHOP had a higher survival rate than that of those receiving CHOP (P<0.01). The expression of RIP2 in DLBCL cell lines was higher than that in peripheral mononuclear cells of normal subjects (P<0.01) and expressed differently in DLBCL of GCB and non-GCB type (P<0.01).</p><p><b>CONCLUSION</b>The expression of RIP2 may relate with the poor prognosis and specific subtype of DLBCL.</p>

Analytical modeling and optimization of herringbone micro-fluidic chip for capture of circulating tumor cells / 医用生物力学

Objective To realize the high-efficient capture of circulating tumor cells (CTCs) in the blood of tumor patients by analytic modeling and optimization on the herringbone micro-fluidic chip. Methods By simulating the fluid flow within the herringbone chip with Fluent 15.0 and calculating the capture efficiency with MATLAB to understand how geometric parameters (the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height), flow rates and flow directions (forward flow, reverse flow) affected the cell-surface contact for capture of the CTCs, the capture efficiency was predicted and then validated by experiments. Results The herringbone micro-fluidic chip could achieve the optimal capture rate when the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height were 75, 125, 70 and 30 μm, respectively, at a flow rate of 1 mL/h with forward direction. Conclusions In this study, cell capture in different micro-fluidic chips was simulated by the method of computational fluid dynamics. The statistic model of capture efficiency is established by MATLAB and optimized to quickly screen a group of physical parameters for high-efficient cell capture. These optimized micro-fluid chip parameters are validated by experiment, which can realize the high-efficient capture of CTCs.

Finite element modeling of proximal femur and element size analysis based on CT images / 医用生物力学

Objective To establish 5 different finite element models of the proximal femur based on CT images, and analyze the influences of element size on materials distribution and biomechanical behavior of the proximal femur model. Methods The proximal femur was scanned by spiral CT. The images, stored as DICOM format, were extracted by Mimics to obtain 3D geometric data, and then meshed separately by Mimics, 3-Matic and ICEM software to establa voxel element model, a tetrahedral element model and 3 hexahedral element model (with element size of 2, 1, 0.5 mm). These meshed models were assigned materials by Mimics, and their mechanical behavior was analyzed by Abaqus eventually. Results For the proximal femur model with material assignment based on CT images, the influence of element size on the total mass of all the 5 models was not significant. The nodal Mises stress and nodal displacement along the same path in 5 models showed a similar tendency, while the Mises stress at each node displayed an obvious deviation. The nodal Mises stress in the hexahedral element model with the element size of 0.5 mm showed accordance with the voxel element model. Conclusions The element size has a small influence on the total mass and nodal displacement when the material assignment is attributed to the model based on CT gray values, while decrease in the element size will affect the materials distributions and stress distributions of the model. When the element size of the proximal femur model is close to its voxel size, the mass distributions and mechanical behavior of the femur can be preferably reflected.

Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA.</p><p><b>METHODS</b>We divided 32 4-week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region.</p><p><b>RESULTS</b>Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3β activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH.</p><p><b>CONCLUSIONS</b>Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt/β-catenin signaling pathway.</p>

Finite element analysis on anterior and posterior internal fixation for treating type ⅡHangman’s fracture / 医用生物力学

Objective To evaluate biomechanical differences between anterior titanium plate internal fixation and posterior pedicle screw internal fixation for treating type Ⅱ unstable Hangman’s fracture by finite element analysis. Methods An intact finite element model of the upper cervical spine (C0-3) was established and validated, and an unstable model was also established. Two different internal fixation models, i.e. anterior titanium plate+Cage with bone graft (Plate+Cage) and C2 pedicle screws+C3 lateral mass screws (C2PS+C3LMS) were established, respectively, based on the unstable model. The vertical load of 40 N was applied on the occiput to simulate head weight and 1.5 N•m torque was applied on the occiput to simulate loading conditions of flexion, extension, lateral bending and rotation. Range of motion (ROM) of C2-3, force pathway and strain at the fractured line were calculated and analyzed. ResultsCompared with the unstable model, the Plate+Cage model could decrease the ROM by 92.4%, 97.1%, 96.5% and 90.0%, while the C2PS+C3LMS model could decrease the ROM by 88.6%, 90.2%, 95.7% and 90.3%, in flexion, extension, lateral bending and axial rotation, respectively. The maximum stress of the Plate+Cage model was smaller than that of the C2PS+C3LMS model under 4 loading conditions. Conclusions The anterior Plate+Cage fixation possesses better stability than the posterior C2PS+C3LMS fixation in flexion and extension, while both fixation methods show similar stability in lateral bending and axial rotation. The anterior Plate+Cage fixation is more reasonable in structure and stress distributions, and can achieve reduction, decompression, fixation and fusion in one step, thus it is an effective operative procedure for treating typeⅡ Hangman’s fracture.

Clinical Control Study of Endoscopic Full-thickness Resection and Laparoscopic Surgery in the Treatment of Gastric Tumors Arising from the Muscularis Propria / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gastric stromal tumors arising from the muscularis propria are located in deeper layers. Endoscopic resection may be contraindicated due to the possibility of perforation. These tumors are therefore usually removed by surgical or laparoscopic procedures. This study evaluated the curative effects, safety and feasibility of endoscopic full-thickness resection (EFR) of gastric stromal tumors originating from the muscularis propria.</p><p><b>METHODS</b>This study enrolled 92 patients with gastric stromal tumors >2.5 cm originating from the muscularis propria. Fifty patients underwent EFR, and 42 underwent laparoscopic intragastric surgery. Operation time, complete resection rate, length of hospital stay, incidence of complications, and recurrence rates were compared in these two groups.</p><p><b>RESULTS</b>EFR resulted in complete resection of all 50 gastric stromal tumors, with a mean procedure time of 85 ± 20 min, a mean hospitalization time of 7.0 ± 1.5 days and no complications. Laparoscopic intragastric surgery also resulted in a 100% complete resection rate, with a mean operation time of 88 ± 12 min and a mean hospitalization period of 7.5 ± 1.6 days. The two groups did not differ significantly in operation time, complete resection rates, hospital stay or incidence of complications (P > 0.05). No patient in either group experienced tumor recurrence.</p><p><b>CONCLUSIONS</b>EFR technique is effective and safe for the resection of gastric stromal tumors arising from the muscularis propria.</p>

Stability analysis of the pelvis and fracture fixation in standing position / 医用生物力学

Objective To develop the three-dimensional (3D) finite element (FE) models of pelvis and fracture fixation, and test their validity. Methods Based on CT scan images, the 3D FE model of the pelvis was built by software of Mimics, ANSYS ICEM, Hypermesh and ABAQUS. A uniformly distributed load of 600 N was applied in vertical direction on the upper lamina of S1 vertebrae to simulate the stresses on the pelvis in standing position and to verify the validity of the pelvis model. T-shaped acetabular fracture models with 3 types of fixation were also established to verify the validity of internal fixation. ResultsBoth the stress and displacement distributions were found to be bilaterally symmetrical on the pelvis in standing position, with the Von Mises stresses mainly distributed in the beginning of arcuate line, pubic branch and posterior-superior area of acetabulum. The largest displacement occurred in the center of the sacral crest, and became relatively smaller in iliac fossa and femur, which was reduced gradually to the femur. Each of the three fixation types in acetabulum showed good biomechanical stability. Conclusions The established hexahedral grid-3D FE model can accurately simulate mechanical properties of the femur in standing position, which would provide an intuitive basis for clinical study.

Response rules of pressing pain on back section in Governor Vessel in patients with gastroesophageal reflux disease / 中国针灸

The response rules of pressing pain on the back section in the Governor Vessel in patients with gastro-esophageal reflux disease (GERD) were studied to provide references for the diagnosis and treatment of GERD. Seventy-six cases of GERD were included into an observation group while 30 healthy volunteers were recruited into a control group. A mechanical measurement device of pressing pain that could measure the pain threshold was adapted to observe the pressing pain on the back section in the Governor Vessel in GERD patients and healthy volunteers. The test area is from spinous process of the 1st thoracic vertebra to that of the 12th thoracic vertebra (T1 -T12), including acupoints and non-acupoints on the Governor Vessel. As a result, in the observation group the pain threshold of T5-T7 spinous process clearance, which was the location of Shendao (GV 11), Lingtai (GV 10) and Zhiyang (GV 9), was lower than that in the control group (all P < 0.05). This result indicated that there was significant pressing pain in T5-T7 spinous process clearance in patients with GERD, which could be taken as an important auxiliary diagnosis and a new thinking method in the treatment of GERD with acupuncture.

Does urothelial cancer of bladder behave differently in young patients? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.</p><p><b>METHODS</b>From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.</p><p><b>RESULTS</b>Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.</p><p><b>CONCLUSIONS</b>Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.</p>

Clinical features on chromophobe renal cell carcinoma / 中华外科杂志

<p><b>OBJECTIVES</b>To explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma.</p><p><b>METHODS</b>From January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations, treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis.</p><p><b>RESULTS</b>All cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases, pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free. The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63.8% and 49.9% at the same periods, and there is no difference in the survival rate of five years (P > 0.05) but significant difference in that of ten years (P < 0.01).</p><p><b>CONCLUSIONS</b>Chromophobe renal cell carcinoma is a morphologically uncommon subtype of renal cell carcinoma with the good prognosis. Definite diagnosis depends on its typical pathological feature. Radical nephrectomy is the first choice for the treatment of chromophobe renal cell carcinoma.</p>

Cardiac mast cells accumulation and degranulation contribute to collagen deposition after coronary microembolization / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate potential pathophysiological role of cardiac mast cells accumulation and degranulation on the collagen deposition after coronary microembolization (CME).</p><p><b>METHODS</b>CME was induced in miniswine by selective infusion of 15X10(4) microspheres (diameter, 45 mum) into the left anterior descending artery groups (CME group, n=8). Some CME-induced animals were pretreated with the MC stabilizer tranilast (50 mg/kg, twice daily), beginning 2 weeks before CME and thereafter throughout the experimental period (CME +tranilast group, n=8), while some animals received tranilast without CME (tranilast group, n=8). Eight sham-operated animals without CME served as controls. After 30 days, the total number of MC and degranulating MCs and collagen deposition was assessed by histological and electronic microscopy studies.</p><p><b>RESULTS</b>The numbers of total and degranulating MCs and collagen volume fraction (CVF) at day 30 in CME group were significantly higher than those in controls (P <0.01). Treatment with tranilast significantly reduced the numbers of total and degranulating MCs and CVF at day 30 (all P <0.01). There was a significant positive correlation of the CVF with the number of total MCs (r=0.91, P <0.001) and degranulating MCs (r=0.92, P <0.001) over the CME myocardium.</p><p><b>CONCLUSION</b>MCs accumulation and degranulating contribute to myocardial fibrosis collagen deposition.</p>

Prevention of hepatic tumor growth and metastasis in rats with rapamycin / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To test the effect of rapamycin (RAPA) on hepatic tumor growth and metastasis in Sprague-Dawley (SD) rat model and explore the possible mechanism.</p><p><b>METHODS</b>SD rat hepatocellular carcinoma (HCC) model with metastatic potential was induced by diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR). 120 SD rats were randomized into four groups 16 weeks after DEN and NMOR treatment, and received 4-week intraperitoneal injection of RAPA (1.5 or 4.5 mg x kg(-1) x d(-1)), CsA (25 mg x kg(-1) x d(-1)) or equal volume of 0.9% saline, respectively. Tumor growth and metastasis were checked after the 4-week treatment. Serum vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay (ELISA). Antiangiogenetic effects were assessed by CD34 immunostaining. The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF proteins and mRNAs were detected by immunohistochemistry, western blot and reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The mean liver weight (5.58% +/- 0.42% and 5.69% +/- 0.74%), the metastatic liver nodules (5.12 +/- 0.68 and 5.67 +/-1.12), the metastasis lung nodules (0.43 +/- 0.11 and 0.45 +/- 0.83), and the lung metastasis rate (17.2% and 14.8%) were lower in rats treated with RAPA 1.5 mg x kg(-1) x d(-1) or 4.5 mg x kg(-1) x d(-1) than those in rats treated with saline, which were 10.42% +/- 1.86%, 12.36 +/- 3.45, 1.81 +/- 0.3 and 50.0% respectively (P < 0.01 or P < 0.05). The intratumoral microvessel density (MVD), serum VEGF, and the levels of HIF-1 alpha and VEGF were lower in RAPA-treated rats than those in control rats. However, CsA-treated rats showed an opposite trend compared with the RAPA-treated rats.</p><p><b>CONCLUSION</b>RAPA can repress the expression of angiogenesis-promoting factors HIF-1 alpha and VEGF, and significantly inhibits the growth and metastasis of HCC.</p>

Construction and preliminary panning of Fab phage display antibody library against respiratory syncytial virus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To construct a human phage display antibody library, which will help to develop new drugs and vaccines against respiratory syncytial virus (RSV) and solve many of the issues that have limited the progression and application of murine monoclonal antibodies (McAbs) in the clinic. This can provide a platform for human antibody preparation and diagnosis, prophylaxis and therapy of RSV infection in children.</p><p><b>METHODS</b>Peripheral blood lymphocytes were isolated from 52 children with RSV infection. cDNA was synthesized from the total RNA of lymphocytes. The light and heavy chain Fd (VH-CH1) fragments of immunoglobulin gene were amplified by RT-PCR. The amplified products were cloned into phagemid vector pComb3x and the clone samples were electrotransformed into competent E.coli XL1-Blue. The transformed cells were then infected with M13K07 helper phage to yield recombinant phage antibody of Fabs. The plasmids extracted from amplified E.coli were digested with restriction endonucleases Sac I, Xba I, Spe I and Xho I to monitor the insertion of the light or heavy chain Fd genes. RSV virions were utilized as antigens to screen Fab antibodies.</p><p><b>RESULTS</b>By recombination of light and heavy chain genes, an immune Fab phage display antibody library against RSV containing 2.08x10(7) different clones was constructed, in which 70% clones had light chains and heavy chain Fd genes. The capacity of Fab phage antibody gene library was 1.46x10(7) and the titre of the original Fab antibody library was about 1.06x10(12) pfu/mL. The antibody library gained an enrichment in different degrees after the preliminary panning.</p><p><b>CONCLUSIONS</b>Utilizing the technology of phage display, an immune Fab phage display antibody library against RSV was successfully constructed in this study, which laid a valuable experimental foundation for further study and created favorable conditions for preparing human McAbs. This may also contribute to the improvement in the diagnosis, therapy and prophylaxis of RSV infection in children.</p>

Effects of the needling method for regulating kidney and smoothing liver on endocrine and immune functions in the patient with hyperplasia of mammary glands / 中国针灸

<p><b>OBJECTIVE</b>To probe into a better acupoint association for treatment of hyperplasia of mammary glands and the mechanism.</p><p><b>METHODS</b>Two hundred cases were randomly divided into a regulating kidney and smoothing liver needling group, a routine acupuncture group and a Chinese medicine group. The regulating kidney and smoot hing liver needling group were treated with acupuncture at Shenshu (BL 23), Mingmen (GV 4), Fengfu (GV 16), Lingxu (KI 24), Shenfeng (KI 23), Bulang (KI 22), Qimen (LR 14), etc. and the routine acupuncture group with acupuncture at Zusanli (ST 36), Tanzhong (CV 17), Ganshu (BL 18), Rugen (ST 18), Neiguan (PC 6), Qimen (LR 14), once daily; and the Chinese medicine group with oral administration of Rupixiao tablet, 6 tablets each time, thrice each day. After they were treated for 2 menstrual cycles, the therapeutic effects and changes of E2, PRL, P, CD3+, CD4+ and CD8+ were observed.</p><p><b>RESULTS</b>The clinical therapeutic effect and the total effective rate for TCM syndromes were 92.0% and 94.0% in the regulating kidney and smoothing liver needling group, 86.0% and 88.0% in the routine acupuncture group and 78.0% and 84.0% in the Chinese medicine group, with a significant difference among the 3 groups, the former being better than the other two groups; after treatment, serum PRL, P, P/E2 significantly improved in all the 3 groups (P < 0.05) and the regulating kidney and smoothing liver needling group was better than other two groups in decreasing PRL and increasing P, P/E2 (P < 0.05); and E2, CD8+, CD4+/CD8+ significantly improved in the regulating kidney and smoothing liver needling group and the routine acupuncture group, the former being better than the later in decreasing E2 (P < 0.05).</p><p><b>CONCLUSION</b>The regulating kidney and smoothing liver needling method is an effective method for treatment of hyperplasia of mammary glands and it has regulative action on endocrine and immune functions in the patient with hyperplasia of mammary glands.</p>