High accuracy measurement of the ground-state hyperfine splitting in a 113Cd+ microwave clock: erratum.

We present an erratum to our Letter [Opt. Lett.40, 4249 (2015)OPLEDP0146-959210.1364/OL.40.004249]. This erratum corrects the nuclear Lande factor gI in Eq. (2). After correcting the error, the final ground-state hyperfine splitting frequency of the 113Cd+ ion is determined to be 15199862855.0287(10) Hz.

Clinical epidemiology and outcome of HIV-associated talaromycosis in Guangdong, China, during 2011-2017.

OBJECTIVES: Talaromycosis is an invasive mycosis endemic to Southeast Asia. This study aimed to investigate the epidemiology, clinical features and prognostic factors of HIV-associated talaromycosis in Guangdong, China. METHODS: We retrospectively evaluated HIV patients hospitalized with histopathology- or culture-confirmed talaromycosis between 2011 and 2017. Factors associated with poor prognosis were identified using logistic regression. RESULTS: Overall, 1079 patients with HIV-associated talaromycosis were evaluated. Both the number and prevalence of talaromycosis among HIV admissions increased from 125 and 15.7% in 2011 to 253 and 18.8% in 2017, respectively, reflecting the increase in HIV admissions. Annual admissions peaked during the rainy season between March and August. Common clinical manifestations included fever (85.6%), peripheral lymphadenopathy (72.3%), respiratory symptoms (60.8%), weight loss (49.8%), skin lesions (44.5%) and gastrointestinal symptoms (44.3%). Common laboratory abnormalities were hypoalbuminaemia (98.6%), anaemia (95.6%), elevated aspartate aminotransferase level (AST) (76.9%), elevated alkaline phosphatase level (55.8%) and thrombocytopenia (53.7%). The median CD4 count was 9 cells/µL. Talaromyces marneffei was isolated from blood and bone marrow cultures of 66.6% and 74.5% of patients, respectively. The rate increased to 86.6% when both cultures were performed concurrently. At discharge, 14% of patients showed worsening conditions or died. Leucocytosis, thrombocytopenia, elevated AST, total bilirubin, creatinine and azole monotherapy independently predicted poor prognosis. CONCLUSIONS: The incidence of HIV-associated talaromycosis has increased in Guangdong with the high HIV burden in China. Skin lesions were seen in less than half of patients. Induction therapy with azole alone is associated with higher mortality. Findings from this study should help to improve treatment of the disease.

[Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage â a1 （LVSI+）-â b1 cervical cancer patients with different tumor size: a big database in China].

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Regulatory functions of trehalose-6-phosphate synthase in the chitin biosynthesis pathway in Tribolium castaneum (Coleoptera: Tenebrionidae) revealed by RNA interference.

RNA interference (RNAi) is a very effective technique for studying gene function and may be an efficient method for controlling pests. Trehalose-6-phosphate synthase (TPS), which plays a key role in the synthesis of trehalose and insect development, was cloned in Tribolium castaneum (Herbst) (TcTPS) and the putative functions were studied using RNAi via the injection of double-stranded RNA (dsRNA) corresponding to conserved TPS and trehalose-6-phosphate phosphatase domains. Expression analyses show that TcTPS is expressed higher in the fat body, while quantitative real-time polymerase chain reaction results show that the expression of four trehalase isoforms was significantly suppressed by dsTPS injection. Additionally, the expression of six chitin synthesis-related genes, such as hexokinase 2 and glutamine-fructose-6-phosphate aminotransferase, was suppressed at 48 and 72 h post-dsTPS-1 and dsTPS-2 RNA injection, which were two dsTPS fragments that had been designed for two different locations in TcTPS open reading frame, and that trehalose content and trehalase 1 activity decreased significantly at 72 h post-dsRNA injection. Furthermore, T. castaneum injected with dsTPS-1 and dsTPS-2 RNA displayed significantly lower levels of chitin and could not complete the molting process from larvae to pupae, revealing abnormal molting phenotypes. These results demonstrate that silencing TPS gene leads to molting deformities and high mortality rates via regulation of gene expression in the chitin biosynthetic pathway, and may be a promising approach for pest control in the future.

[Clinical application of combined hepatic artery resection and reconstruction in surgical treatment for hilar cholangiocarcinoma].

Objective: To clarify whether the surgical treatment for hilar cholangiocarcinoma combined with artery reconstruction is optimistic to the patients with hilar cholangiocarcinoma with hepatic artery invasion. Methods: There were 384 patients who received treatment in the First Affiliated Hospital to Army Medical University from January 2008 to January 2016 analyzed retrospectively. There were 27 patients underwent palliative operation, 245 patients underwent radical operation, radical resection account for 63.8%. Patients were divided into four groups according to different operation method: routine radical resection group(n=174), portal vein reconstruction group (n=47), hepatic artery reconstruction group (n=24), palliative group(n=27). General information of patients who underwent radical operation treatment was analyzed by chi-square test and analysis of variance. The period of operation time, blood loss, the length of hospital stay and hospitalization expenses of the radical operation patients were analyzed by one-way ANOVA. Comparison among groups was analyzed by LSD-t test. Results: The follow-up ended up in June first, 2016. Each of patients followed for 6 to 60 months, the median follow-up period was 24 months. 1-, 3-, and 5-year survival rates were 81.3%, 44.9% and 13.5% of routine radical operation group, and were 83.0%, 44.7% and 15.1% of portal vein reconstruction group, and were 70.8%, 27.7% and 6.9% of hepatic artery reconstruction group, respectively. And 1-, 3-, and 5-year survival rates of hepatic artery reconstruction group was lower than routine radical group and portal vein reconstruction group significantly (P<0.05). However, the rate of postoperative complications of the hepatic artery reconstruction group and the routine radical operation group and the portal vein reconstruction group were 62.5%(15/24), 55.3%(96/174) and 51.5%(24/47), respectively. There was no significant difference among them (P>0.05). The data shows that the ratio of lymphatic metastasis in hepatic artery reconstruction group (70.8%) is much higher than them in routine radical operation group (20.1%) and portal vein reconstruction group (19.1%) significantly (P<0.05). The presented data also indicate that hepatic artery resection prolongs survival time comparing with patients undergoing palliative therapy for hilar cholangiocarcinoma. Cox regression analysis indicate that hepatic artery resection and reconstruction is a protective factor compare with palliative therapy (RR=0.38, 95%CI: 0.22-0.67). The significant reason for shorter survival time is a positive correlation between hepatic artery invasion and lymph node metastasis. Conclusion: Hepatic artery resection and reconstruction has beneficial impact on oncologic long-term outcome in patients with advanced stage hilar cholangiocarcinoma.

[Clinical investigation of ultrasound-guided percutaneous nephrolithotomy accessed by SVOF-principle and two-step puncture techniques].

Objective: To evaluate the safety and effectiveness of ultrasound-guided percutaneous nephrolithotomy (PCNL) accessed by SVOF-principle and two-step puncture techniques. Methods: A total of 838 cases with upper urinary stones underwent percutaneous nephrolithotomy successfully accessed by ultrasound-guided between June 2007 and December 2015 at Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Of all cases were divided in two groups: hydronephrosis calyces puncture group include 425 cases and SVOF-principle puncture group include 413 cases. The access establishment time, operation time, stone free rate (SFR), postoperative complications, and postoperative hospitalization time between the two groups we compared by t test or χ2 test. Results: Statistically significant differences were observed between hydronephrosis calyces puncture group and SVOF-principle puncturegroup in the first access establishment time ((16.5±8.4) minutes vs. (11.2±5.9) minutes, t=3.931, P=0.013), one-stage SFR (74.3% vs. 85.7%, χ2=16.868, P=0.000), postoperative hospitalization time ((6.4±2.1) days vs. (4.8±1.8)days, t=4.574, P=0.000), transfusion rate (7.1% vs. 2.9%, χ2=8.027, P=0.006), and embolization rate (3.3% vs. 1.0%, χ2=5.390, P=0.020). There were no statistically significant differences in operation time, total SFR, postoperative fever and sever infection between these two groups (all P>0.05). In both two groups, no serious complications such as peripheral organ injury and death occurred. Conclusions: PCNL accessed guided by ultrasound with SVOF-principle and two-step puncture techniques has advantages of quick puncture location, high stone free rate, fewer complications and fast recovery. This technique is an effective and safe treatment option for upper urinary stones and deserved promotion and application in clinic.

Immunofluorescence reveals unusual patterns of labelling for connexin43 localized to calbindin-D28K-positive interstitial cells in the pineal gland.

Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 µm) or as unusually large pools of Cx43 ranging up to 4-7 µm in diameter or length. These puncta and pools were highly concentrated in perivascular spaces, where they were associated with numerous cells devoid of labelling for markers of pinealocytes (e.g. tryptophan hydroxylase and serotonin), and where they were minimally associated with blood vessels and lacked association with resident macrophages. Astrocytes labelled for glial fibrillary acidic protein were largely restricted to the anterior pole of the pineal gland, where they displayed only fine and sparse Cx43-puncta along their processes. Labelling for Cx43 was localized largely though not exclusively to the somata and long processes of a subpopulation of perivascular interstitial cells that were immunopositive for calbindin-D28K. These cells were often located among dense bundles or termination areas of sympathetic fibres labelled for tyrosine hydroxylase or serotonin. The results indicate that interstitial cells form abundant gap junctions composed of Cx43, and suggest that gap junction-mediated intracellular communication by these cells supports the activities of pinealocytes.

Connexin36 localization to pinealocytes in the pineal gland of mouse and rat.

Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein and mRNA has been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36-containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat. Immunofluorescence labelling of Cx36 was visualized exclusively as puncta or short immunopositive strands that were distributed throughout the pineal, and which were absent in pineal sections from Cx36 null mice. By double immunofluorescence labelling, Cx36 was localized to tryptophan hydroxylase-positive and 5-hydroxytryptamine-positive pinealocyte cell bodies and their large initial processes, including at intersections of those processes and at sites displaying a confluence of processes. Labelling for the cell junction marker zonula occludens-1 (ZO-1) either overlapped or was closely associated with labelling for Cx36. Pinealocytes thus form Cx36-containing gap junctions that also incorporate the scaffolding protein ZO-1. FRIL revealed labelling of Cx36 at ultrastructurally defined gap junctions between pinealocytes, most of which was at gap junctions having reticular, ribbon or string configurations. The results suggest that the endocrine functions of pinealocytes and their secretion of melatonin is supported by their intercellular communication via Cx36-containing gap junctions, which may now be tested by the use of Cx36 null mice.

Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and lacks an effective treatment. The disease pathogenesis has not been clarified at present. Pathological transactive response DNA-binding protein 43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE (antioxidant responsive element) signaling dysfunction, we constructed an ALS cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid-transfected NSC-34 cells were rounded with reduced neurites, shortened axons, increased levels of intracellular lipid peroxidation products, and decreased viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidant capacity of NSC-34 cells and increased their susceptibility to oxidative damage. We further showed that expression of the MafK protein and the Jun dimerization protein 2 (JDP2) was reduced in TDP-43-M337V plasmid-transfected NSC-34 cells, which might cause accumulation of Nrf2 in nuclei but a decrease in NQO1 expression. Taken together, our results confirmed that TDP-43-M337V impaired the Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and provided information for further research on the molecular mechanisms of TDP-43-M337V in ALS.

False-positive cytopathology results for papillary thyroid carcinoma: A trap for thyroid surgeons.

OBJECTIVES: Current preoperative diagnosis of thyroid nodules remains imperfect despite recent advances in cytopathology and molecular diagnostics. False positivity in preoperative fine-needle aspiration cytology (FNAC) may lead to overtreatment of patients, including total thyroidectomy, and sometimes to lawsuits for misdiagnosis and malpractice. In this study, we analysed clinical characteristics and pathologic findings in patients with false positivity for papillary thyroid carcinoma (PTC) in FNAC. METHODS: We retrospectively reviewed permanent pathology results from 3788 patients who underwent thyroid surgery. Among them, 48 patients had lesions that were deemed suspicious or positive (Bethesda class V or VI) for PTC in preoperative FNAC. We reviewed clinic-pathologic data, radiologic findings and surgical planning in these patients. RESULTS: The prevalence of pathologic thyroiditis was significantly higher among patients with false-positive FNAC results than in those with confirmed PTC (54.2% vs 9.2%, P<.001). The analysis of the permanent pathology reports showed that 26 patients had chronic lymphocytic thyroiditis and 22 patients had no evidence of thyroiditis. Among the patients without pathologic thyroiditis, 19 patients (86.4%) had nodular hyperplasia and three (13.6%) had follicular adenoma, while among the patients with pathologic thyroiditis, seven (26.9%) had no nodule, 14 (53.8%) had nodular hyperplasia, two (7.7%) had hyalinized nodules, two (7.7%) had follicular adenoma and one (3.8%) had a hyalinizing trabecular tumour. In 42 patients, the extent of surgery (total thyroidectomy or hemithyroidectomy) was to be determined according to the intra-operative frozen section biopsy results. Among them, four (10.5%) had inconclusive frozen section results, and 38 (90.5%) had benign results on frozen section. CONCLUSIONS: Patient counselling about the possibility of false positivity is still important. And the presence of thyroiditis might create confusion in the interpretation of cytopathologic results.