[Clinical features and prognoses of re-operated patients for persistent/recurrent papillary thyroid carcinoma].

Objective: To investigate the clinicopathological characteristics and the survival of re-operated patients for persistent/recurrent papillary thyroid carcinoma (PTC) and risk factors for re-recurrence after the second operation. Method: A retrospective analysis of 69 cases underwent re-operation for persistent/recurrent PTC in Sichuan Cancer Hospital from January 2010 to December 2016 was performed. There were 21 males and 48 females, aged 14-85 (44.8) years old. According to the imaging after initial treatment, they were divided into a recurrence group (42 cases) and a persistent disease/residual group (27 cases). The positive rates of ipsilateral paratracheal lymph node metastases at re-operation were calculated and compared by chi-square test. Patients were divided into different subgroups according to potential risk factors for re-recurrence. Kaplan-Meier (K-M) method was used for survival analysis. Results: The positive rate of ipsilateral paratracheal lymph node metastasis in recurrence group (15/42, 35.7%) was significantly lower than that in the persistent disease/residual group (17/27, 63.0%) (χ2=4.91, P<0.05). The follow-up period after re-operation was 60-104 months, with a median of 66 months, and 8 patients were lost to follow-up. Permanent hypoparathyroidism occurred in 2 cases (2.9%) and permanent recurrent laryngeal nerve palsy in 1 case (1.4%). Twenty patients had structural recurrences and/or distant metastases. The 5-year disease-specific survival rate was 92.8% and the 5-year recurrence-free survival rate was 68.1%. Survival analysis was performed on risk factors such as age≥55 years old, recurrent tumor diameter ≥4 cm, number of positive lymph nodes ≥ 10, and obvious extracapsular invasion (ENE). Among them, age and diameter of recurrent tumor had significant influences on recurrence-free survival rate (χ2 was 6.36, 8.17, respectively, both P values<0.05). There was a statistically significant difference in recurrence-free survival rates between ENE(+) group and ENE(-) group (χ2=5.52, P<0.05). Conclusion: For the re-operated patients due to persistence/ recurrence PTC, attention should be paid to protecting the parathyroid gland and recurrent laryngeal nerve during re-operation. Timely and effective postoperative follow-up for patients aged ≥ 55 years, with recurrent tumor diameter ≥ 4 cm and ENE(+), can significantly improve their prognoses.

[Treatment of lumbar degenerative diseases with recapping laminoplasty and nerve root canal's decompression preserving the continuity of supraspinous ligament].

Objective: To explore the clinical effect of lumbar discectomy and nerve root canal's enlargement preserving the continuity of supraspinous ligament in the treatment of lumbar degenerative disease. Methods: The data of patients with lumbar degenerative disease who underwent operation from 2016 to 2018 were analyzed retrospectively, and the patients were divided into two groups according to the different operation. The treatment group (17 cases) was treated with recapping laminoplasty, lumbar discectomy and nerve root canal's enlargement, and the control group (28 cases) was treated with total laminectomy, nerve root canal's enlargement, lumbar discectomy, interbody fusion and internal fixation (PLIF). All patients were followed up for 12 to 27 months (mean 17.8 months). Japanese Orthopaedic Association Scores(JOA) and visual analogue scale(VAS) of pain were used to evaluate the clinical effect before and after the operation, lumbar dynamical X-ray and Cobb angle were collecting for imaging evaluation, and the adjacent segment degeneration at the last follow-up was recorded. Results: There was no significant difference in preoperative JOA score, VAS score and Lumbar Cobb angle between the two groups (all P>0.05). The operation time in the treatment group was shorter than that in the control group, and the blood loss during operation in the treatment group was lower than that in the control group, the bed rest time of the treatment group after operation was shorter than that in the control group ((79±14) vs (118±17) min, (151±38) vs (324±70) ml and (3.4±0.7) vs (4.3±1.0) d,respectively; t=-8.508, -10.724, -3.244, all P<0.01). In addition, compared with the control group, the volume of postoperative drainage in the treatment group also decreased significantly (t=-5.637, P<0.01). There was no significant difference in JOA score between the two groups 1 year after the operation (P>0.05), but there was significant difference in VAS score between the two groups, the treatment group was better than the control group (P<0.05). Compared with the control group, the lumbar Cobb angle in the treatment group increased significantly one year after the operation (55.3°±3.2° vs 38.4°±6.2°, t=10.391, P<0.05). During the follow-up, no loosening or fracture of the implants was found in all patients. Conclusion: Treatment of lumbar degenerative diseases with recapping laminoplasty and nerve root canal's decompression preserving the continuity of supraspinous ligament by ultrasound osteotome has the same clinical effect as PLIF. It has the advantages of shortening operation time, less bleeding, better maintenance of lumbar lordosis after operation and reduction of adjacent segment degeneration.

[Clinical safety and efficiency of ultrasonic bone curette used in anterior cervical discectomy and fusion surgery].

Objective: To investigate the safety and efficiency of ultrasonic bone curette used in anterior cervical discectomy and fusion surgery. Methods: As a retrospective study, we collected and analyzed the clinical data of 47 patients receiving anterior cervical discectomy and fusion surgery in Luohe Central Hospital from January 2014 to January 2017, there were 26 males and 21 females with a mean age of (52±9) years. According to the different surgical tools used in the process of decompression by resecting osteophytes or bone like an inverted Chinese character "" located at the posterior margin of the vertebral body, the patients were divided into two groups: ultrasonic bone curette group (group A) and traditional tools group (group B). The operating time, volume of intraoperative blood losing, complications, Japanese Orthopedic Association (JOA) score before and after the operation and improvement rate were recorded in the two groups. The t test was used to compare the data between the two groups. Results: In group A, the operating time was (47±7) min, blood loss was (49±4) ml, 1 case experienced urinary tract infection and there was no cerebrospinal fluid leakage or spinal cord injury. In group B, the operating time was (54±12) min and the blood loss was (117±16) ml, cerebrospinal fluid leakage occurred in 2 patients and the incision healed one-stage by local compression, hoarseness happened in 1 case and it disappeared after 2 weeks, 2 patients had swallowing discomfort and recovered in one month, no spinal cord injury occurred in this group. The operating time and blood loss in group A were lower than those in group B (t=2.691, 20.704, both P<0.05). And the incidence of complications in group A were lower than that in group B (χ(2)=4.157, P=0.041). The JOA score of group A at 3 days after surgery was improved for 39.0% when compared with that before the surgery, and it was improved for 71.6% at one year after the surgery. The JOA score in group B at 3 days after surgery was elevated for 38.7% from that before the surgery, and it increased for 69.4% at one year after the surgery. There was no significant different in JOA score before the surgery, 3 days and one year after the surgery between the two groups (t=0.611, 1.076, 0.061, all P>0.05). Conclusion: In the process of decompression by resecting osteophytes or bone located at the posterior margin of the vertebral body in the anterior cervical discectomy and fusion surgery, ultrasonic bone curette is safe and effective, and it can effectively shorten the operating time, decrease the blood loss and cut down the incidence of complications.

MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-ß/Smad pathway.

OBJECTIVE: To explore whether MOTS-c could improve osteoporosis by promoting osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) via transforming growth factor-ß (TGF-ß)/Smad pathway. MATERIALS AND METHODS: Rat BMSCs were isolated and cultured, followed by osteogenic and lipid differentiation. CCK-8 (cell counting kit-8) assay was performed to detect the highest treatment dose of MOTS-c that did not affect cell proliferation. Expressions of osteogenesis-related genes (ALP, Bglap, and Runx2) were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction) and Western blot, respectively. Alizarin red staining and alkaline phosphatase (ALP) cytochemical staining were carried out to evaluate the effect of MOTS-c on BMSCs osteogenesis. TGF-ß/Smad pathway-related genes (TGF-ß1, TGF-ß2, and Smad7) in BMSCs treated with MOTS-c were detected. Finally, TGF-ß1 was knocked down to investigate the regulatory effect of MOTS-c on BMSCs osteogenesis. RESULTS: BMSCs exhibited an elongated morphology and was identified with a high purity by flow cytometry. After osteogenic differentiation, alizarin red staining and ALP staining were all positive. MOTS-c treatment could remarkably stimulate the formation of calcified nodules in BMSCs. Besides, TGF-ß/Smad pathway-related genes were significantly upregulated after BMSCs were treated with MOTS-c. Promoted osteogenesis by MOTS-c treatment was reversed by the TGF-ß1 knockdown. CONCLUSIONS: MOTS-c promotes cell differentiation of BMSCs to osteoblasts via TGF-ß/Smad pathway.

Isotope Effect in Tunneling Ionization of Neutral Hydrogen Molecules.

It has been recently predicted theoretically that due to nuclear motion light and heavy hydrogen molecules exposed to strong electric field should exhibit substantially different tunneling ionization rates [O. I. Tolstikhin, H. J. Worner, and T. Morishita, Phys. Rev. A 87, 041401(R) (2013)]. We studied that isotope effect experimentally by measuring relative ionization yields for each species in a mixed H_{2}/D_{2} gas jet interacting with intense femtosecond laser pulses. In a reaction microscope apparatus, we detected ionic fragments from all contributing channels (single ionization, dissociation, and sequential double ionization) and determined the ratio of total single ionization yields for H_{2} and D_{2}. The measured ratio agrees quantitatively with the prediction of the generalized weak-field asymptotic theory in an apparent failure of the frozen-nuclei approximation.

Up-regulation of telomerase in human B lymphocytes occurs independently of cellular proliferation and with expression of the telomerase catalytic subunit.

Telomerase activity is up-regulated 1000-fold higher in human tonsil germinal center B cells compared to resting naive or memory B cells, and telomerase expression can be re-activated in vitro resting B cells. To understand the mechanism(s) of telomerase regulation, quiescent B cell from peripheral blood or tonsil were activated with different combinations of various stimuli. Cross-linking surface (s)IgD or sIgM of B cells induced marked up-regulation of telomerase enzymatic activity in the absence of cellular proliferation. Low level cross-linkage of surface molecules by soluble anti-IgM did not up-regulate the telomerase activity. However, the inability of soluble anti-IgM to up-regulate the telomerase activity was corrected by additional signals from soluble anti-CD40 antibody engagement or IL-4 / IL-10. Activation of B cell proliferation with Epstein-Barr virus failed to up-regulate telomerase, further suggesting that up-regulation of telomerase is an event independent of B cell proliferation. Telomerase induction occurred in the late G1 phase of the cell cycle and did not require entry into S phase. Up-regulation of telomerase enzymatic activity correlated primarily with the induction of expression of the hTERT gene, the catalytic subunit to telomerase, suggesting that control of telomerase regulation resides at the level of the catalytic subunit of this holoenzyme.

Telomerase is up-regulated in human germinal center B cells in vivo and can be re-expressed in memory B cells activated in vitro.

The extensive proliferation that B lymphocytes undergo in germinal centers could compromise generation of long term B cell memory if there occurs shortening of the telomeres of germinal center B cells with cell division. Telomere length, which is thought to act as a "mitotic clock" for somatic cells that dictates cellular senescence, can be preserved by the enzyme telomerase. Human tonsil germinal center B cells consistently expressed 100- to 1000-fold higher levels of telomerase activity than naive or memory B cells, which had no or very low detectable activity, as analyzed by the telomere repeat amplification protocol assay. In vitro stimulation of human memory B cells through surface Ig or CD40 was capable of up-regulating telomerase. The findings suggest that longevity of B cell memory is maintained, despite multiple cell divisions in the generation of a memory B cell, by up-regulation of telomerase in germinal center and activated memory B cells.

Expression of the F glycoprotein gene from human respiratory syncytial virus in Escherichia coli: mapping of a fusion inhibiting epitope.

A cDNA copy of the gene encoding the entire amino acid sequence of the fusion (F) protein of human respiratory syncytial virus (strain A2) was inserted into a bacterial expression vector containing the lambda PR promoter. Upon heat induction, Escherichia coli cells harboring the vector produced a 45-kDa peptide which reacted with rabbit polyclonal antiserum to the native F protein. Expression of the F gene resulted in severe inhibition of bacterial growth, which was overcome by deletion of the DNA sequences encoding the F signal peptide. The region of the F protein which reacted with a virus-neutralizing and fusion-inhibiting monoclonal antibody was probed by expressing cDNA fragments encoding different protein domains in E. coli and testing antibody reactivity by Western blot analysis. Analysis of six fragments yielded an overlapping antibody-reactive region between amino acids 253 and 298. Analysis of reactivity with a cassette of synthetic peptides confirmed that the virus-neutralizing epitope mapped between residues 289 and 298 defined by the amino acid sequence M-S-I-I-K-E-E-V-L-A.

Mapping of a fusion related epitope of the respiratory syncytial virus fusion protein.

The region of the fusion glycoprotein of respiratory syncytial virus which reacts with a neutralizing and fusion inhibiting monoclonal antibody, was mapped using a deductive method derived from analysis of Western blot reactivity of proteolytic fragments. Reaction of the whole fusion protein was found to be so conformationally dependent, that complete digestion of the protein with a variety of proteases resulted in fragments which were not sufficiently reactive to permit mapping. For this reason, polyclonal antibodies to synthetic peptides which spanned the fusion protein sequence, were used to map the position of large peptides derived from partial digests, and these peptides were then analysed for their ability to react with the monoclonal antibody. Comparison of the peptides which were reactive with the monoclonal antibody to those which were not, identified a region of non-overlap between residues 283 and 327 in the F1 subunit of the fusion protein. Synthesis of a peptide within this region confirmed the placement of the epitope.