Search

Objective: Previous trials demonstrated the effectiveness of exercise in improving pain and functional impairment in patients with knee osteoarthritis (KOA). However, a bibliometric analysis of top-cited papers on exercise treatment for KOA has not yet been conducted. The aim of the present study was to critically analyze the bibliometric characteristics of the most frequently cited articles on exercise treatment for KOA., Materials and Methods: Publications about exercise treatment for KOA from 2000 to 2021 were searched from the Web of Science database. Two authors independently collected 100 top-cited articles, and a consensus was reached to form the final list. The title, journal, author, year of publication, country and institution of origin, total citations, citations in 2021, main topics, research nature, and level of evidence were extracted, and the publication trends in exercise treatment for KOA were evaluated., Results: A total of 1,258 papers were retrieved from the database. According to the final list, clinical research accounted for 81% of the studies, but no statistical difference in the number of citations was found among the four types of articles (p=0.194). Seventy articles had a level of evidence of Ib, and no statistical differences in citations were found per level of evidence (p=0.767). Most of the top-cited articles were published between 2005-2014, and Dr Messier was the prominent writer in this field., Conclusions: This bibliometric study is the first to identify the most cited papers in exercise treatment for KOA research. Traditional Chinese exercise, comorbidity, and exercise adherence may be the next popular research trends that will receive more attention in the future.

Objective: To determine the association of SOX2 with the prognosis in lung cancer, studies providing survival information were selected based on multivariate Cox regression analysis., Material and Methods: PubMed, Embase, and Web of Science databases were searched to identify eligible studies before June 19, 2021. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated to assess the prognostic impact of SOX2 based on multivariate Cox regression analysis. Publication bias was used to assess the risk of bias. Functional analysis of SOX2 was also conducted., Results: 13 studies with a total of 2008 patients with lung cancer were included. SOX2 expression was not correlated with overall survival in lung cancer (10 studies with 1591 cases). Between-study heterogeneity was noted (I 2 =85.6%, p<0.0001). Subgroup analysis suggested that no correlation was found between SOX2 expression and overall survival in non-small cell lung cancer (NSCLC: eight studies with 1319 cases) and small-cell lung cancer (SCLC: two studies with 272 cases). SOX2 expression was significantly associated with worse time-to-progression (two studies with 104 cases: HR=3.50, 95% CI=1.34-9.15) and recurrence-free survival (two studies with 335 cases: HR=1.45, 95% CI=1.12-1.87) in NSCLC. Function analysis demonstrated that SOX2 was involved in DNA repair, cell cycle, regulation of stem cell population maintenance, and Hippo signaling pathway., Conclusion: SOX2 may be an independent prognostic factor in time-to-progression and recurrence-free survival and may become a promising therapeutic target. More studies are essential to further our findings., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Seven Fusarium species complexes are treated, namely F. aywerte species complex (FASC) (two species), F. buharicum species complex (FBSC) (five species), F. burgessii species complex (FBURSC) (three species), F. camptoceras species complex (FCAMSC) (three species), F. chlamydosporum species complex (FCSC) (eight species), F. citricola species complex (FCCSC) (five species) and the F. concolor species complex (FCOSC) (four species). New species include Fusicolla elongata from soil (Zimbabwe), and Neocosmospora geoasparagicola from soil associated with Asparagus officinalis (Netherlands). New combinations include Neocosmospora akasia, N. awan, N. drepaniformis, N. duplosperma, N. geoasparagicola, N. mekan, N. papillata, N. variasi and N. warna. Newly validated taxa include Longinectria gen. nov. , L. lagenoides , L. verticilliforme , Fusicolla gigas and Fusicolla guangxiensis . Furthermore, Fusarium rosicola is reduced to synonymy under N. brevis. Finally, the genome assemblies of Fusarium secorum (CBS 175.32) , Microcera coccophila (CBS 310.34), Rectifusarium robinianum (CBS 430.91), Rugonectria rugulosa (CBS 126565), and Thelonectria blattea (CBS 952.68) are also announced here. Citation: Crous PW, Sandoval-Denis M, Costa MM, Groenewald JZ, van Iperen AL, Starink-Willemse M, Hernández-Restrepo M, Kandemir H, Ulaszewski B, de Boer W, Abdel-Azeem AM, Abdollahzadeh J, Akulov A, Bakhshi M, Bezerra JDP, Bhunjun CS, Câmara MPS, Chaverri P, Vieira WAS, Decock CA, Gaya E, Gené J, Guarro J, Gramaje D, Grube M, Gupta VK, Guarnaccia V, Hill R, Hirooka Y, Hyde KD, Jayawardena RS, Jeewon R, Jurjević Ž, Korsten L, Lamprecht SC, Lombard L, Maharachchikumbura SSN, Polizzi G, Rajeshkumar KC, Salgado-Salazar C, Shang Q-J, Shivas RG, Summerbell RC, Sun GY, Swart WJ, Tan YP, Vizzini A, Xia JW, Zare R, González CD, Iturriaga T, Savary O, Coton M, Coton E, Jany J-L, Liu C, Zeng Z-Q, Zhuang W-Y, Yu Z-H, Thines M (2022). Fusarium and allied fusarioid taxa (FUSA). 1. Fungal Systematics and Evolution 9 : 161-200. doi: 10.3114/fuse.2022.09.08., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© 2022 Westerdijk Fungal Biodiversity Institute.)

We report an unusual pressure-induced superconducting state that coexists with an antiferromagnetic ordering of Eu 2+ moments and shows a large upper critical field comparable to the Pauli paramagnetic limit in EuTe 2 . In concomitant with the emergence of superconductivity with T c  ≈ 3-5 K above P c  ≈ 6 GPa, the antiferromagnetic transition temperature T N (P) experiences a quicker rise with the slope increased dramatically from dT N /dP = 0.85(14) K/GPa for P ≤ P c to 3.7(2) K/GPa for P ≥ P c . Moreover, the superconducting state can survive in the spin-flop state with a net ferromagnetic component of the Eu 2+ sublattice under moderate magnetic fields μ 0 H ≥ 2 T. Our findings establish the pressurized EuTe 2 as a rare magnetic superconductor possessing an intimated interplay between magnetism and superconductivity., (© 2022. The Author(s).)

Objective: Current evidence of the maternal, perinatal and neonatal outcomes in twin pregnancies among mothers with advanced age is unclear, especially for mothers with age above 40 years., Materials and Methods: A systematic search was conducted using the PubMed, Scopus, and Google Scholar databases. Studies that were observational in design or analysed retrospective data were considered for inclusion. The included studies had to be conducted in twin pregnancies and should have documented the effect of maternal age on obstetric and/or neonatal outcomes. Statistical analysis was performed using STATA software., Results: A total of 20 studies were considered for inclusion. All the studies were based on retrospective data. Compared to mothers aged under 40 years, those with advanced age (≥40 years) had increased risk of caesarean delivery [RR 1.20, 95% CI: 1.05, 1.37], gestational hypertension [RR 2.71, 95% CI: 1.72, 4.27], gestational diabetes mellitus [RR 2.03, 95% CI: 1.28, 3.21], preterm birth [RR 2.47, 95% CI: 1.09, 5.80], neonatal admission to intensive care unit [RR 1.78, 95% CI: 1.21, 2.64] and perinatal and/or neonatal mortality [RR 5.76, 95% CI: 1.11, 29.7]. The risk of gestational diabetes mellitus [RR 1.52, 95% CI: 1.21, 1.90] and having caesarean delivery [RR 1.19, 95% CI: 1.10, 1.28] was higher in mothers with ≥35 years of age, compared to those <35 years. There were no significant differences in the risk of adverse neonatal outcomes among the mothers with age ≥35 years. However, in these mothers, the risk of perinatal/neonatal mortality [RR 0.82, 95% CI: 0.76, 0.88] was comparatively lower than in mothers under 35 years of age. There appeared no significant risk of advanced maternal age for postpartum haemorrhage, hospitalization during pregnancy and premature rupture of membranes., Conclusions: The increased risk of maternal, neonatal and perinatal outcomes in mothers with advanced age highlights the need for close follow-up, early detection and management of medical complications in twin pregnancies.

Abstract: Objective To construct a polymerase chain reaction-capillary electrophoresis （PCR-CE） detection method using ChlB gene and NIES gene, investigate the method's specificity and sensitivity, and to evaluate its application value in drowning diagnosis. Methods The specific primers ChlB and NIES were designed for the conserved sequence of chlorophyte ChlB gene and cyanophyte NIES gene in GenBank to construct PCR-CE detection method; 50 species of standard DNA samples were amplified; the sensitivity was determined by gradient concentration detection of positive standard samples; 25 actual cadaver lung tissue samples （drowned： 20, natural death： 5） were detected, and the simultaneous detection results of microwave digestion-vacuum filtration-automated scanning electron microscopy （MD-VF-Auto SEM） were simultaneously compared. Results The minimum DNA detection concentration of primers ChlB and NIES was 0.161 ng and 0.109 ng, respectively, which could specifically amplify chlorophyte （Chlorella pyrenoidosa） and cyanophyte ［Microcystis aeruginosa （producing and not producing toxin）］ widespread in water. The product fragments were 156 bp and 182 bp, respectively. The results of non-drowning tissues were negative. Conclusion This method has high sensitivity and specificity. It can be applied to the detection of plankton related to drowning and combined with MD-VF-Auto SEM method, can increase the detection range of plankton related to drowning and improve the evidence power of drowning diagnosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods: A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results: The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type Ⅳ collagen α3, α4, α5 chains immunofluorescence and skin type Ⅳ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl's grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions: The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS ( P <0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system( P <0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system ( P <0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

Objective: Previous studies have shown that microRNA-765 (miR-765) is involved in certain biological behaviors of human cancers. However, abnormal expression and function of miR-765 have not been reported in osteosarcoma (OS)., Patients and Methods: Changes in the expression of miR-765 and MTUS1 (Microtubule-associated tumor suppressor 1) were examined via Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The function of miR-765 was investigated through Cell Counting Kit-8 (CCK-8) and transwell assays in OS. The target of miR-765 was identified using a Dual-Luciferase reporter assay., Results: MiR-765 was upregulated in OS tissues. And upregulation of miR-765 promoted cell proliferation, migration and invasion in OS. In addition, MTUS1 was confirmed as a direct target gene of miR-765. Moreover, miR-765 promoted the progression of OS through targeting MTUS1. Furthermore, miR-765 was involved in tumorigenesis of OS through activating extracellular-signal-regulated kinase/ epithelial-mesenchymal transition (ERK/EMT) pathway., Conclusions: MiR-765 targets MTUS1 to promote the progression of OS via mediating the ERK/EMT pathway. Therefore, miR-765 may be used as a novel biomarker for the diagnosis of OS.

Purpose: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments., Methods: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments., Results: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups., Conclusion: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

Objective: To evaluate the patients with Cardiac amyloidosis (CA) and Hypertrophic cardiomyopathy (HCM) by using the strain indexes of three-dimensional speckle tracking imaging(3D-STI) technique, and to evaluate the prognosis. Methods: A total of 32 patients with pathologically confirmed cardiac amyloidosis and 34 patients with hypertrophic cardiomyopathy and 16 normal controls were enrolled from the First Affiliated Hospital of Zhejiang University College of Medicine from June, 2013 to January, 2018.The color Doppler echocardiography and three-dimensional speckle tracking echocardiography were used to measure strain indexes of each group, and the Logistic regression equation was used to analyze the index differences.The cut-off values were analyzed using the Receiver Operating Characteristic (ROC), and Kaplan-Meier and Cox were used for survival regression analysis. Results: The globe radial strain (GRS) (16%±7% vs 23%±9%), left ventricular wall peak time difference (PSD) (52 ms±17 ms vs 77 ms±25 ms), Sokolow-Lyon index (20 mm±6 mm vs 34 mm±14 mm) were significantly different between cardiac amyloidosis group and hypertrophic cardiomyopathy group by 3D-STI, which had high sensitivity and specificity by Logistic regression analysis.The area under the ROC curve of GRS was 0.725, PSD was 0.812, Sokolow-Lyon index was 0.832.In addition, the area strain and atrial septal thickness were significant prognostic factors according to survival regression analysis. Conclusions: For the differential diagnosis of cardiac amyloidosis with preserved LVEF, unlike echocardiographic parameters, the 3D-STI strain indicators could be used to differentiate cardiac amyloidosis from hypertrophic cardiomyopathy, reflecting obvious diagnostic advantages.When combined with area strain and atrial septal thickness, 3D-STI strain indicators could be used to predict the survival prognosis, which are important in clinical practice.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion: This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

In April 2016, an outbreak emerged in a cultured population of black-spotted pond frog tadpoles in Shuangliu County, China, whereas tadpoles were suffering from substantial mortality (90%). Principal clinical signs of diseased tadpoles were comprised haemorrhage on their body surface, swollen abdomen with yellow ascites, congestion and swelling of the liver. The diseased tadpole's homogenates tissue were inoculated into epithelioma papulosum cyprini (EPC) cells at 25 °C for 4 days which caused typical cytopathic effect, and the viral titer TCID 50 reached 10 7 /0.1 mL. In pathogenicity tests, tadpoles were immersed in 2‰ virus fluid for 8 h, the clinical signs were observed similar to those recognized in naturally infected tadpoles and mortality rate were reached up to 80%, which affirms that the virus was the main cause for this disease. In addition, transmission electron microscopy of EPC cells infected with isolated virus reflected that the virus was in a regular hexagon way (shape) with capsule like structure. The diagonal diameter was recorded 135 ± 8 nm, wherever virus particles were arrayed in crystalline manner in the cytoplasm. The electrophoresis of MCP gene PCR-product showed that the samples of diseased tadpoles, aquaculture water source and isolated virus were all positive. The sequence of the isolate revealed more than 99% similarities to ranavirus based on homology and genetic evolution analysis of the whole MCP gene, and the isolate belongs to FV3-like virus group. This study confirmed that ranavirus was the causative agent of this outbreak, and named the virus as Rana nigromaculata ranavirus (RNRV)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: PTENP1, a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. The relationship between PTENP1 and susceptibility tumors is reported, while, an association of PTENP1 with the risk of oral squamous cell carcinoma (OSCC) in Chinese population is lacked. This research is designed to investigate the association of PTENP1 with susceptibility of OSCC., Patients and Methods: In this research, TaqMan technology was used to test genotype in 342 OSCC patients and 711 healthy controls, so as to analyze the association between PTENP1 polymorphisms (rs7853346 rs865005 and rs10971638) and susceptibility of oral squamous cell carcinoma., Results: The results of this research showed that rs7853346 [Additive model: Adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.66-0.99] was related to the OSCC risk. It was not found that the other two sites were associated with the susceptibility of OSCC., Conclusions: This research indicated that rs7853346 is statistically correlated with the OSCC risk.

Objective: To investigate the overall efficacy of early breast cancer after breast-conserving treatment. To analyze risk factors affecting local regional recurrence (LRR), distant metastasis (DM) and survival. Methods: 1 791 breast cancer patients treated with breast-conserving surgery were retrospectively analyzed. The inclusion criteria were pathologic diagnosis of invasive breast cancer without supraclavicular and internal mammary node metastasis, T1-2N0-3M0, and no neoadjuvant therapy. Univariate analysis of survival was performed by Kaplan-Meier method and log rank test. Cox regression model was used for multivariate analysis. Results: The median follow-up time was 4.2 years. For all patients, the 5-year LRR, DM, disease-free survival(DFS) and overall survival(OS) rates were 3.6%, 4.6%, 93.0% and 97.4%, respectively. The LRR rates of patients with Luminal A, Luminal B1, Luminal B2, HER-2 over-expressed and triple-negative breast cancer were 2.0%, 6.1%, 5.9%, 0 and 10.0%, while the DM rates were 3.2%, 6.7%, 8.3%, 4.8% and 7.3%, respectively. Among the N0 patients, axillary dissection was performed in 689 cases and sentinel lymph node biopsy in 652 cases. The 5-year LRR rates were 3.3% and 3.2% ( P =0.859), and the OS rates were 98.2% and 98.3% ( P =0.311) respectively, which showed no statistically significant. There were 1 576 patients that underwent postoperative radiotherapy. Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone (2.5% vs 12.9%). The 5-year LRR rates of patients who received conventional fractionated radiotherapy and hypo-fractionated radiotherapy were 2.7% and 3.1%, respectively. But the difference was not statistically significant ( P =0.870). Multivariate analysis showed that age, lymphovascular invasion, pathological T staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors of LRR in breast cancer patients (all P <0.05). Histological grade and pathological N staging were independent factors of DM (all P <0.05). The age, lymphovascular invasion, pathological T and N staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors for DFS (all P <0.05). Histological grade, pathological N staging, ER/PR status and endocrine therapy were factors for OS (all P <0.05). Conclusions: With contemporary standard treatment, the recurrence rate of early breast cancer after breast conserving treatment is less than 10%. Node-negative patients after sentinel lymph node biopsy did not need axillary dissection. The overall utilization of radiotherapy after breast conserving surgery is satisfactory. Hypofractionated radiotherapy is as effective as conventional fractionated radiotherapy. Local regional recurrence and distant metastasis have different risk factors.

Objective: To analyze the clinical features and prognosis of the ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery. Methods: From 1999 to 2013, 63 women with IBTR after breast conserving surgery were retrospectively reviewed. All patients had adequate information on tumor location both at first presentation and at recurrence, with or without regional recurrence or distant metastasis. The histologic changes between true local recurrence and elsewhere recurrence groups were compared. The local recurrence, the overall survival after IBTR (IBTR-OS), the disease-free survival after IBTR (IBTR-DFS) were also compared. Results: All patients had undergone lumpectomy, including 38 cases with additional axillary lymph node dissection and 13 cases with sentinel lymph node biopsy. There were 11.3% (7/63) cases received neoadjuvant systemic therapy, 68.3% (43/63) had adjuvant radiotherapy, 60.3% (38/63) underwent adjuvant chemotherapy and 47.6% (30/63) received hormonal therapy. Forty-five cases (71.4%) had recurrence in the same quadrant, and 18 cases (28.6%) had elsewhere recurrence. Compared with histology at presentation, 10.3% of the patients (6/58) had different ones at recurrence and 28.9% of patients (13/45) had different molecular subtypes. The conversion rate of estrogen receptor status (33.3% vs 9.5%, P =0.012) and progesterone receptor status (56.3% vs 19.0%, P =0.005) in patients with elsewhere recurrence was significantly higher than that in patients with same quadrant recurrence. Fifty-nine cases had undergone surgery after IBTR, with 48 cases of secondary breast-conserving surgery and 11 cases of salvage mastectomy. The median time to IBTR of same quadrant recurrence and elsewhere recurrence groups were 26 months and 62 months ( P =0.012), respectively. There were 84.4% and 44.4% cases who had local recurrence within 5 years after breast conserving surgery, respectively. Of all cases, the overall 5-year IBTR-OS and 5-year IBTR-DFS rates were 79.4% and 60.4%, respectively. There were no significant differences in 5-year IBTR-OS (77.4% vs. 83.6%, P =0.303) or 5-year IBTR-DFS (60.0% vs. 62.8%, P =0.780) between same quadrant recurrence and elsewhere recurrence groups. Univariate analysis showed that pN0-1 ( P <0.001), luminal subtype ( P =0.026), adjuvant endocrine therapy ( P =0.007) at first presentation, recurrent tumor < 3 cm ( P =0.036) and having surgery after IBTR( P =0.002) were favorable factors of IBTR-OS. pN0-1 ( P <0.001) at first presentation, recurrent tumor stage Ⅰ-Ⅱ ( P <0.001) and having surgery after IBTR( P =0.001) were favorable factors of IBTR-DFS. There was no significant difference between second breast-conserving surgery and salvage mastectomy in IBTR-OS and IBTR-DFS ( P >0.05). Conclusions: The IBTR after breast conserving surgery mainly occurred at the original quadrant. Second breast-conserving surgery did not affect patient's prognosis. There were significant differences in biological features between the same quadrant recurrence and elsewhere recurrence, requiring different therapeutic strategies in the future.

Objective: To investigate the prevalence and characteristics of pathogenic variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome (aHUS). Method: Eleven Han Chinese children with aHUS, including 9 boys and 2 girls aged between 1 year and 4 months and 13 years, were investigated in Department of Pediatrics, Fuzhou General Hospital, from November 1998 to February 2014. Analysis of variants of all the exons of 10 complement genes (CFH, MCP, CFI, C3, CFB, CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5), including 25 bases from 3' end and 25 bases from 5' end, was performed in the 11 cases by targeted sequence capture and next generation sequencing. Significant variants detected by next generation sequencing were confirmed by Sanger sequencing. To understand pathogenicity of variants found in the captured genes, we investigated genetic conservation by multiple protein sequence alignment among different species, and analyzed whether the variants were located in protein domains or not, and investigated functional significance by functional computational prediction methods. Result: Twenty-seven percent of Han Chinese children with aHUS carried pathogenic variants in the 10 complement genes. Pathogenic variant CFB 221G>A (R74H) was detected in Patient 3 and Patient 9, which was not found in parents of Patient 3' , and was found in healthy father of patient 9. Pathogenic variant CFHR5 242C>T (P81L) was found in Patient 2, and was found in healthy father of patient 2. However, no pathogenic variants in genes CFH, MCP, CFI, C3, CFHR1, CFHR2, CFHR3 and CFHR4 were identified. Conclusion: Pathogenic variants in the 10 complement genes were identified in 3/11 of Han Chinese children with aHUS in our study and CFB was the most frequently mutated gene.

Objective: To analyze the outcomes of clinical T1-3N1M0 breast cancer patients with pathological negative axillary lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) and mastectomy, and investigate the role of postmastectomy radiotherapy (PMRT). Methods: A total of 185 patients with clinical T1-3N1M0 breast cancer treated between 1999 and 2013 were retrospectively reviewed. All patients were treated with NAC and mastectomy, and achieved ypN0. Of them, 89 patients received additional PMRT and 96 patients did not. 101 patients had clinical stage Ⅱ disease. 84 patients had clinical stage Ⅲ disease. The rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. Univariate analysis was used to interpret the impact of clinical features and treatment on patients' outcome. Results: The 5-year rates of LRR, DM, DFS, and OS for all patients were 4.5%, 10.4%, 86.6%, and 97.1%, respectively. For patients with and without PMRT, the 5-year LRR rates were 1.1% and 7.5% ( P =0.071), the 5-year DM rates were 5.1% and 15.0% ( P =0.023), the 5-year DFS rates were 95.0% and 79.0% ( P =0.008), and the 5-year OS rates were 100.0% and 94.5% ( P =0.089) respectively. In univariate analysis, lymph-vascular space invasion (LVSI) was poor prognostic factor of LRR ( P =0.001), < 40 years old and lack of PMRT was a poor prognostic factor for DM ( P <0.05), lack of PMRT was a poor prognostic factor for DFS ( P =0.008), primary lesion residual and mild-moderate pathological response to NAC were poor prognostic factors for OS ( P <0.05). In the subgroup of Stage Ⅲ disease, for patients with and without PMRT, the 5-year LRR rates were 1.9% and 14.4% ( P =0.041), the 5-year DFS rates were 91.9% and 67.4% ( P =0.022), respectively. In the subgroup of Stage Ⅱ disease, for patients with and without PMRT, the 5-year DM rates were 0 and 11.5% ( P =0.044), the 5-year DFS rates were 100.0% and 84.9% ( P =0.023), respectively. Conclusions: The LRR rate of clinical T1-3N1M0 breast cancer patients who achieved ypN0 after NAC and mastectomy was low. PMRT decreased the DM rate and increased DFS rate in all patients, and significantly decreased the LRR rate in Stage Ⅲ disease. PMRT should be considered for patients with Stage Ⅲ disease, and further research is warranted to investigate the benefit of PMRT for Stage Ⅱ disease.

Purpose: Primary insomnia is a persistent and recurrent disorder as well as a risk factor for depression. The aim of this study was to determine whether the zolpidem combined with paroxetine would be effective in the treatment of patients with primary insomnia., Methods: Ninety patients meeting DSM-IV criteria for primary insomnia were randomly assigned to 8 weeks of treatment with zolpidem combined with paroxetine (the combined treatment group, n = 45) or zolpidem combined with placebo (the control group, n = 45). Patients were assessed with the Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG), and the Treatment Emergent Symptom Scale (TESS)., Results: Compared with the control group, the combined treatment group was more significantly improved on wake time after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE), and total PSQI scores, but not the sleep onset latency (SOL)., Conclusions: Eight weeks of the zolpidem combined with paroxetine treatment to patients with primary insomnia is more effective than zolpidem treatment only in sleep maintenance and early morning awakenings.

Objective: To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups., Methods: From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures., Results: The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns., Conclusions: This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

Purpose: The purpose of this retrospective study was to investigate whether Stage IIIC (TanyN3M0) breast cancer can be classified further into subgroups with different prognosis., Materials and Methods: One hundred and thirty-two patients with Stage IIIC breast cancer at Tianjin Medical University Cancer Institute and Hospital were analyzed. The disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method for lymph node ratio (LNR) and the number of positive lymph node (PLN). The receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of the LNR and PLN. The univariate and multivariate analysis were applied to identify the prognostic factors., Results: The results showed that the optimal cut-off value of LNR value was 0.65, and the optimal cut-off value of PLN was 15. The Kaplan-Meier survival analysis showed the higher value of LNR or PLN was correlated with shortened DFS (P = 0.002, P = 0.008, respectively) and OS (P < 0.001, P = 0.001, respectively). In multivariate survival analysis, the value of LNR and PLN were still remained as independent prognostic factors for DFS (P = 0.014, P = 0.013, respectively) and OS (P = 0.004, P = 0.002, respectively)., Conclusion: These results suggest that the value of LNR or PLN could be used as a new significant prognostic biomarker for Stage IIIC breast cancer patients. Stage IIIC breast cancer patients with lower value of LNR or PLN may be down staged.

Objectives: To analyse the lung metastasis and possible factors influencing lung metastasis in alveolar soft part sarcoma (ASPS) patients., Methods: The medical records of 64 consecutive ASPS patients were reviewed to analyse their treatments, features of lung metastasis, and possible factors influencing lung metastasis., Results: Thirty-six females and 28 males with a median age of 27 years were included. The primary disease sites were the extremities in 51 patients and other locations in 13 patients. The median primary tumour size was 5 cm. Wide local excision of the primary tumour was performed on 56 patients (87.5 %). Thirteen patients (20.3 %) received postoperative adjuvant radiotherapy, and nine patients (14.1 %) underwent adjuvant chemotherapy. Twelve patients (18.8 %) presented with metastatic lung disease. Twenty-nine patients (45.3 %) developed metastatic lung disease during follow-up. Lung metastasis occurred in 64.1 % of the patients. Lung metastasis was detected at a median interval of 20 months after primary ASPS diagnosis. Being male, >20 years of age, having a primary tumour size ≥ 5 cm, and local recurrence were associated with a greater rate of lung metastasis. Median survival after the diagnosis of lung metastasis was 34 months. The 5-year survival rates were 64.1 and 95.2 % for patients with and without lung metastasis (P < 0.001). Thirty-seven patients with metastatic lung disease received anthracycline- and ifosfamide-based chemotherapy. One patient experienced a partial remission., Conclusions: ASPS patients have a high prevalence of lung metastasis. Sex, age, primary tumour size, and local recurrence are major factors influencing lung metastasis. Chemotherapy is not efficacious in ASPS patients with lung metastasis.

Environmental influences on the development and progression of dental caries are well known; however, there is little evidence of a genetic component imparting susceptibility to dental caries. The aim of this study was to investigate the relationship between a single nucleotide polymorphism in the vitamin D receptor TaqI locus and dental caries susceptibility in a Chinese population. This case-control study was conducted with a case group (264 patients with dental caries from northwestern China) and a control group (219 individuals without dental caries or systemic disease from the same area). DNA was extracted from the peripheral venous blood of the study participants; the distribution of TaqI locus genotypes and allele frequencies was determined via polymerase chain reaction-restriction fragment length polymorphism. The data obtained were statistically analyzed using the Hardy-Weinberg equilibrium and Chi-square test. The frequency of the Tt genotype in the case group (14.0%) was significantly higher than that in the control group (4.3%), as determined using the genotype TT as the reference. The risk of dental caries was increased 3.8-fold in individuals with the heterozygous Tt genotype compared to that in the individuals with the TT genotype. The proportion of the 't' allele in the case group (7.0%) and the control group (2.1%) was observed to be significantly different [P = 0.0003; OR = 3.592, confidence interval 95% (1.790-7.208)]. Our results therefore suggested that the allele 't' might be a genetic factor determining dental caries susceptibility in individuals from the northwest of China.

Objective: The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown., Materials and Methods: Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment., Results: Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response., Conclusions: These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.

The aim of this study was to investigate the selection of plasma exchange (PE) parameters and the safety of children with severe ricinism. The PE parameters and heparin dosage in 7 children with severe ricinism were recorded, and changes in the patients' vital signs and coagulation function were monitored before and after PE. All patients successfully completed PE. The speed of blood flow was 50-80 mL/min, speed of exchange flow was 600-800 mL/h, and isolating rate of blood plasma was 12.5-19.05%. Transmembrane pressure was stable at approximately 100 mmHg, and venous pressure was stable at approximately 95 mmHg. The first dose of heparin was 0.39 ± 0.04 mg/kg, and the maintaining heparin dose was 0.40 ± 0.05 to 0.22 ± 0.03 mg·kg(-1)·h(-1). During the PE process, mean arterial pressure, heart rate, respiratory rate, and pulse oxygen saturation were steady. After PE, the activated partial thromboplastin time and thrombin time prolonged to 2-3 times greater than that before PE. However, no bleeding tendency was seen. For children with severe ricinism, the choice of PE to eliminate the toxin from blood, tissues, and organs was safe and effective.

Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents.

Mutations in the Wilms' tumor suppressor gene (WT1) can lead to syndromic forms of steroid-resistant nephrotic syndrome (SRNS) such as Denys-Drash or Frasier syndrome and can cause isolated SRNS. A mutation within WT1 is a frequent cause of sporadic isolated SRNS in girls. In a worldwide cohort of girls, the rate of occurrence was 10.8%. Previous reports have indicated that in Chinese girls, the detection rate of WT1 mutations is 16.7% for early onset isolated nephrotic syndrome. The detection rate of WT1 mutations in Chinese girls with sporadic isolated SRNS is unknown. We examined WT1 mutations in 14 Chinese girls with sporadic isolated SRNS using polymerase chain reaction and direct sequencing and studied a control group of 38 boys with sporadic isolated SRNS. We identified a WT1 mutation in 1 of 14 (7.1% detection rate) Chinese girls with sporadic isolated SRNS. No mutations occurred in WT1 in the remaining 13 girls or the control group. Our investigation supports the necessity of genetic examination for mutations in WT1 in girls with sporadic isolated SRNS.

Airway smooth muscle (ASM) cell phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca(2+) levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this system's involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-α increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-α-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-α-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-α-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IκBα. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-α-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's binding to the M3R and the downstream activation of NF-κB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Since the identification of the NPHS1 gene, which encodes nephrin, various investigators have demonstrated that the NPHS1 mutation is a frequent cause of congenital nephrotic syndrome (CNS); it is found in 98% of Finnish children with this syndrome and in 39-80% of non-Finnish cases. In China, compound heterozygous mutations in the NPHS1 gene have been identified in two Chinese families with CNS. To our knowledge, however, whether or not NPHS1 is the causative gene in sporadic Chinese CNS cases has not been established. We identified a homozygous mutation of NPHS1, 3250insG (V1084fsX1095), in a Chinese child with sporadic CNS. This finding leads us to suggest that NPHS1 mutations are also present in sporadic Chinese CNS cases. This gives additional support for the necessity for genetic examination of mutations in the NPHS1 gene in Chinese children with sporadic CNS.

Background: Extranodal nasal-type NK (natural killer)/T-cell lymphoma in elderly patients is rare, and its prognosis is unclear. This study aims to investigate the clinical characteristics and prognosis of this lymphoma., Patients and Methods: We analyzed 24 patients (age, >60 years old) with early-stage extranodal nasal-type NK/T-cell lymphoma. Among these patients, 23 received radiotherapy alone (n = 15) or radiotherapy and chemotherapy (n = 8) and 1 received chemotherapy alone., Results: Elderly patients with early-stage extranodal nasal-type NK/T-cell lymphoma were characterized by male predominance, good performance, large proportion of localized disease, more comorbidities, low-risk international prognostic index, and unfavorable prognosis. The 5-year cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) rates for all patients were 54.3%, 42.0%, and 40.2%, respectively. The 5-year CSS, OS, and PFS rates were 43.5%, 36.6%, and 34.1% in patients who received radiotherapy alone, and 50%, 50%, and 50% in patients who received radiotherapy and chemotherapy, respectively (P = 0.852 for CSS, P = 0.801 for OS, and P = 0.694 for PFS). Four patients died of treatment-related mortality., Conclusion: Elderly patients with early-stage extranodal nasal-type NK/T-cell lymphoma exhibit poor prognosis and need special attention because of high treatment-related mortality.

An amperometric glucose biosensor was successfully developed by electrochemical polymerization of p-chlorophenol (4-CP) at a Pt electrode in the presence of glucose oxidase. The amperometric response of this biosensor to hydrogen peroxide, formed as the product of enzymatic reaction, was measured at a potential of 0.6 V (vs. SCE) in phosphate buffer solution. The performances of sensors, prepared at different monomer concentrations and polymerization potentials, were investigated in detail. The biosensor prepared under optimal conditions had a linear response to glucose ranging from 2.5 x 10(-4) to 1.5 x 10(-2) mol L(-1) with a correlation coefficient of 0.997 and a response time of less than 2 s. Substrate selectivity of the polymer-based enzyme electrode was tested for coexisting interferents such as uric acid and ascorbic acid, and no discernible response was observed. After 90 days, the response of the biosensor remained almost unchanged, indicating very good stability.

The multifractal nature of drop breakup in the air-blast nozzle atomization process has been studied. We apply the multiplier method to extract the negative and the positive parts of the f(alpha) curve with the data of drop-size distribution measured using dual particle dynamic analyzer. A random multifractal model with the multiplier triangularly distributed is proposed to characterize the breakup of drops. The agreement of the left part of the multifractal spectra between the experimental result and the model is remarkable. The cause of the distinction of the right part of the f(alpha) curve is argued. The fact that negative dimensions arise in the current system means that the spatial distribution of the drops yielded by the high-speed jet fluctuates from sample to sample. In other words, the spatial concentration distribution of the disperse phase in the spray zone fluctuates momentarily, showing intrinsic randomness.

Background: This study was conducted to determine whether the paranasal extension of a primary non-Hodgkin's lymphoma (NHL) of the nasal cavity has any deleterious effect on patient outcome., Methods: One hundred and seventy-five patients with previously untreated nasal NHL were reviewed. There were 2 with low grade, 107 with intermediate grade, 17 with high grade, and 49 with unclassifiable lymphomas. In 48 cases the immunophenotype was available and 46 were T-cell lymphoma. According to the Ann Arbor system, there were 133 patients with Stage IE, 28 with Stage IIE, 4 with Stage IIIE, and 10 with Stage IVE lymphomas. Stage IE was subdivided into limited Stage IE (i.e., confined to the nasal cavity [67 patients]) or extensive Stage IE (i.e., presenting with extension beyond the nasal cavity [66 patients]). For patients with limited Stage IE disease the treatment of choice was radiotherapy with or without chemotherapy. In patients with extensive Stage IE disease, treatment was comprised of a combination of chemotherapy and radiotherapy or radiotherapy alone. For patients with a more advanced stage of disease (IIE-IVE), chemotherapy was an integral part of the treatment and was completed by irradiation, especially for patients with Stage IIE disease., Results: The actuarial overall survival (OS) and disease free survival (DFS) rates at 5 years for the whole group were 65% and 57%, respectively. The 5-year OS and DFS rates were influenced by stage, with a gradual decrease from 75% and 68% for Stage IE disease to 35% and 28% for Stage IIE disease, and 31% and 19% for Stage IIIE/IVE disease. Patients with limited Stage IE disease survived significantly longer (90% 5-year OS) compared with those with extensive Stage IE disease (57% 5-year OS; P < 0.001). For 67 patients with limited Stage IE disease, the 5-year OS was 89% with radiotherapy alone and 92% with radiotherapy and chemotherapy, whereas for 66 patients with extensive Stage IE disease, the 5-year OS was 54% with radiotherapy and 58% with combined modality therapy or chemotherapy (P > 0.05)., Conclusions: The prognosis of patients with primary NHL of the nasal cavity is stage dependent. In this large cohort of Stage IE patients, it was demonstrated that the paranasal local extension was a significant prognostic factor associated with poorer treatment outcome. The authors believe that Ann Arbor Stage IE should be subclassified further into limited and extensive Stage IE. The addition of chemotherapy did not appear to modify significantly the survival of patients with either limited or extensive Stage IE disease. The extranodal progression observed in patients with extensive Stage IE and Stage IIE-IVE disease clearly illustrates the need for improvement of systemic treatment.

The circadian melatonin rhythm with high levels in the dark period is important for the synchronization of reproductive response to appropriate environmental conditions in animals. The target sites of melatonin action on reproductive functions remain to be clarified. Using autoradiography (ARG) and radioreceptor binding assays with 2[125I]iodomelatonin, a melatonin agonist, as the radioligand, studies on the sites of melatonin action have increased significantly in the last ten years. The recent cloning of melatonin receptor subtypes also allowed the characterization of receptor(s) to the molecular level. Earlier reports have documented that the hypothalamic-pituitary axis plays a vital role in the regulation of reproduction by melatonin. This is supported in part by the demonstration of melatonin receptors in the suprachiasmatic nuclei (SCN) in the brain and pars tuberalis (PT) in the pituitary. However, the nature of SCN and PT involvement in the reproductive action of melatonin remains unknown. In addition to the hypothalamus and pituitary, the two classical sites of melatonin action, other targets have been identified. The recent demonstration of 2[125I]iodomelatonin binding sites or melatonin receptors in the testis, epididymis, vas deferens, prostate, ovary and mammary gland suggest the concept of multiple sites of melatonin action on the reproductive system. The presence of melatonin receptors in the said tissues is consistent with earlier reports of direct melatonin actions on different levels of the reproductive system. This multiple levels of melatonin action, from the hypothalamus, pituitary, gonads to other reproductive tissues form a robust system of photoperiodic control in animal reproduction. This would guarantee successful gestation and delivery of the offspring at a time with optimum food availability and ultimately favourable for the survival of species. Molecular and cellular studies of melatonin signaling system(s), its regulation and effects on downstream functional events in the future may provide new insights and directions for the study of the physiology and pharmacology of fertility and contraception in animals and humans.

Alterations of autocrine function of pulmonary arterial smooth muscle cells (PASMCs) might play an important role in development of hypoxic pulmonary hypertension (HPH). To test this hypothesis, the effects of hypoxia on angiotensin II (AT II) secretion by cultured new born bovine PASMCs were investigated. AT II secretion decreased significantly when PASMCs were incubated under 2.5% O2 hypoxic condition for 3 to 48 h (P < 0.01 vs control), but decreased further under anoxic condition (P < 0.01 vs control and 2.5% O2 group). Nitric oxide (NO) donor SIN-1 inhibited AT II secretion significantly under normoxic condition, but NO synthase inhibitor L-nitro-arginine (LNA) eliminated the inhibitory effect of anoxia on AT II autocrine and promoted AT II release. It was also found that the concentration of cGMP in PASMCs increased significantly (P < 0.01) at 24 h incubation in 0% O2, an effect that can be attenuated by LNA. Hypoxia stimulated 3H-TdR incorporation of PASMCs significantly (P < 0.001), while captopril exerts an inhibition in normoxic condition (P < 0.001), but without effect under hypoxic condition. The above results suggest that hypoxia can inhibit AT II secretion by inducing endogenous NO production in PASMCs. AT II autocrine is not involved in hypoxic proliferation of PASMCs, but a decrease of AT II may contribute to prevention of the development of HPH.

Vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) are structurally and functionally closely connected. Their interactions may play important roles in the development of hypoxic pulmonary artery hypertension. In the present study, mitogenic regulations between cultured new bovine pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) under both normoxic and hypoxic conditions were investigated. Cell proliferation was assessed by 3H-thymidine incorporation and flow cytometry. Normoxic conditioned medium (CM) from cultured PASMCs inhibited 3H-thymidine incorporation of PAECs by 58% (P < 0.01), but normoxic or hypoxic CM from PAECs promoted or inhibited 3H-thymidine incorporation of PASM by 60% and 27% respectively (P < 0.01). When mixed PAECs and PASMCs were cultured for 24 h, relative 3H-thymidine incorporation of the mixed cells decreased by 22% (P < 0.01 vs monoculture) under normoxic condition, and increased by 75% or 44% under 0% O2 or 2.5% O2 (P < 0.01 vs normoxic mixculture). When PAECs and PASMCs were cocultured in either normoxic or hypoxic conditions, proliferation of PAECs was inhibited while that of PASMs was stimulated significantly (P < 0.01), as compared with that of homotypic cultured cells. These findings suggest that PAECs and PASMCs may mutually regulate their proliferation each other, and this mutual modulation may be changed under hypoxic condition.

The testes of different classes of animals (mammals, birds, reptiles and amphibia) were weighed. Some species showed inconsistent left-right asymmetric testicular weights, while other species (including amphibians, reptiles, some birds and some mammals) showed consistent asymmetry in their weights. In rodents, for example, five strains of mice consistently exhibited asymmetrical testes, with the right testis always being heavier than the left. In contrast, another strain of mice showed inconsistent bilateral asymmetry of the testes.

It has been nearly three decades since the beginning of nationwide research into gossypol as a male antifertility agent in China. Several lines of data implicating some side effects of gossypol were published which led to the termination of this area of research in China. The present review re-examines these data and points out the confusion surrounding issues such as hypokalaemia, irreversible azoospermia and other side effects. The prospects and related difficulties for gossypol as a potential male contraceptive are also discussed.

The effects of hypoxia on the bovine pulmonary arterial smooth muscle cell (PASM) proliferation and serotonin transporter gene expression were investigated using 3H-Thymidine incorporation, immunocytochemical staining and mRNA dot blot hybridyzation, the results were as follows, PASM 3H-Thymidine incorporation increased in response to anoxia for 24 h (P < 0.05). The anoxia-induced increased in DNA synthesis of PASM was significantly stimulated by 5-HT (100, 10 and 1 mumol/L) (P < 0.001), but 5-HT did not increase 3H-TdR incorporation under normoxic condition. Immunocytochemical reaction of serotonin in PASM under normoxic condition was markedly stronger than that of anoxic PASM (P < 0.001). Dot blot analysis showed hypoxia increased serotonin transporter mRNA expression of PASM (P < 0.01). These results indicate that stimulation of PASM proliferation with enhanced serotonin transporter gene expression and high consumption of 5-HT in hypoxia or/and anoxia may take part in the development of hypoxic pulmonany hypertention.

Purpose: To analyze the clinical characteristics, prognosis, and treatment outcome of pelvic cryptorchid seminoma (PCS), and to determine whether whole abdominal-pelvic irradiation for Stage I disease is necessary., Methods and Materials: From 1958 to 1991, 60 patients with PCS were treated at the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing. They presented with a lower abdominal mass and showed a predominance for the right side. A high proportion of patients with PCS [26 of 60 (43%)] had metastatic disease, compared to 20% of those with scrotal seminoma, and there was a tendency toward a higher frequency of pelvic nodal metastases. There were 34 Stage I, 6 Stage IIA, 11 Stage IIB, 5 Stage III, and 4 Stage IV patients. Of these 60 patients, 56 underwent laparotomy with or without cryptorchiectomy (37 radical orchiectomy, 7 partial orchiectomy, and 12 biopsy of the primary or cervical node), and 4 cervical node biopsy only. All patients were further treated with radiotherapy, chemotherapy, or a combination of both. Patients with Stage I and II disease received radiotherapy, whereas patients with Stage III and IV were treated with chemotherapy., Results: The overall and disease-free survivals at 5 and 10 years were 92% and 87%, and 88% and 84%, respectively. The 5- and 10-year survivals were 100% for Stage I, 94% and 87% for Stage II, and 56% and 42% for Stage III/IV, respectively (p < 0.05). Volume of irradiation, i.e., whole abdominal-pelvic radiotherapy (10 patients), versus hockey-stick encompassing paraaortic, ipsilateral iliac nodes and the primary tumor or tumor bed (17) did not influence outcome in Stage I patients. Five patients relapsed within 2-12 years after treatment, and four of these patients were successfully salvaged. Four patients developed a second malignant tumor and died., Conclusion: Stage I and II PCS can be adequately controlled by radiotherapy regardless of the surgical procedure. Whole abdominal-pelvic irradiation for Stage I and IIA disease is not required, and fields can be limited to the paraaortic, ipsilateral iliac nodes and primary tumor or tumor bed. We recommend platinum-based chemotherapy for Stage IIB-IV PCS.