[Clinical analysis of 11 cases of lymphoma complicated with paraneoplastic neurological syndrome].

Objective: To evaluate the clinical characteristics, treatment, and prognosis of patients with paraneoplastic neurological syndrome (PNS) associated with lymphoma. Methods: Between January 2012 and May 2021, the clinical data of 11 patients with lymphoma complicated with PNS treated at Peking Union Medical College Hospital were retrospectively reviewed. Results: Among the 11 patients (8 male and 3 female) , the median onset age was 61 (range, 33-78) years. The symptoms of PNS preceded lymphoma in 10 patients. The median time from the onset of PNS to the diagnosis of lymphoma was 4 months. Of the 11 patients, one had Hodgkin's lymphoma, 8 had B-cell non-Hodgkin's lymphoma, and 2 had peripheral T-cell lymphoma. Seven patients were evaluated for onconeural antibody, of whom 2 were positive (1 for anti-Ma2 antibody and 1 for anti-Yo antibody) . Of the 11 patients, the PNS symptoms of 3 patients were located in the central nervous system, 4 were located in the peripheral nervous system, and 3 were located in the muscle. Eight of the 11 patients were treated with glucocorticoid-based immunosuppressive therapy before the diagnosis of lymphoma. Patients with central nervous system involvement and dermatomyositis responded well to glucocorticoid, whereas patients with peripheral neuropathy did not significantly benefit. All 11 patients were treated with chemotherapy after the diagnosis of lymphoma. The efficacy of chemotherapy was assessed in 9 patients, 7 cases achieved complete remission, 1 case was evaluated as stable disease, and 1 case was evaluated as disease progression. The PNS symptoms of the patients who achieved complete response were almost completely recovered. The median follow-up time was 42 (range, 4-95) months. At the end of the follow-up period, 6 of the 11 patients survived, 3 were lost to follow-up, and 2 died. The median overall survival of the whole group was not reached. Conclusions: PNS can involve various parts of the nervous system and can be associated with different types of lymphoma. Through early diagnosis and treatment, the PNS symptoms could improve in most patients who achieve complete remission of lymphoma.

[Clinical characteristics and prediction model of early death in severe/very severe aplastic anemia with immunosuppressive therapy].

Objective: Early death (ED) characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia (SAA/VSAA) treated with intensive immunosuppression therapy and establish an ED prediction model. Methods: The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin (ATG) at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected. The characteristics and causes of ED within 90 days were analyzed retrospectively. Cox proportional hazards model was used to screen the ED risk factors and build a prediction model. Results: Only 19 patients (8.2% ) developed ED with a median time of 24 (3-85) days among the 232 patients with SAA/VSAA who received ATG treatment. The main cause of ED was infection (84.2% ) , followed by cerebral hemorrhage (10.5% ) . Multivariate analysis showed that VSAA (HR=15.359, 95% CI 1.935-121.899, P=0.010) , fungal infection prevention by posaconazole (HR=0.147, 95% CI 0.019-1.133, P=0.066) , lymphocyte count (LYM) ≤ 0.5×10(9)/L (HR=3.386, 95% CI 1.123-10.206, P=0.030) , and PLT ≤ 5×10(9)/L (HR=8.939, 95% CI 1.948-41.019, P=0.005) were ED's independent influencing factors. To build a clinical prediction model, VSAA, fungal infection prevention by posaconazole, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L were scored with 3, -2, 1, and 2, respectively. The integral model AUC=89.324 (95% CI 80.859-97.789) . The ED risk in patients with a score ≥ 3 was 23.1 (95% CI 5.3-100.2) times that in patients with a score<3. Conclusion: ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG. VSAA, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

[Effect of partial cricotracheal resection and extended cricotracheal resection for severe laryngotracheal stenosis].

Objective: To assess the outcomes of partial cricotracheal resection (CTR) and extended cricotracheal resection (ECTR) for severe laryngotracheal stenosis. Methods: From November 2009 to September 2017, 18 patients underwent CTR and ECTR at the Department of Otorhinolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University for severe laryngotracheal stenosis were reviewed retrospectively. There were 12-male and 6-female patients, with the age ranged from 4 to 56 years (median 25 years). The causes were postintubation in 11 cases, cervical trauma in 4, idiopathic in 3. The stenosis located in subglottic and tracheal (n=12), glottic and subglottic and tracheal (n=3), subglottic (n=2), and glottic and subglottic (n=1). Two patients had concurrent unilateral vocal cord palsy.One patient had undergone previous endoscopic balloon dilation and 8 patients had previous laryngotracheal reconstruction. The stenosis was graded according to modified Myer-Cotton classification as follows: Ⅲb (n=1), Ⅲc(n=1), Ⅳa (n=2), Ⅳb (n=12), Ⅳc (n=2). The surgical outcomes and complications were recorded. Results: Among 18 patients,11 of the 12 patients undergoing CTR were decannulated. Five of the 6 patients undergoing ECTR were decannulated. Resected airway length ranged from 1.5 to 4.0 cm (median 2.8 cm). Surgical complications included infection of incision wound in 2 cases, anastomotic granulation in 2, cervical subcutaneous emphysema in 1, aspiration in 1, and unilateral arytenoid prolapse in 1. No recurrent laryngeal nerve injury or tracheoesophageal fistula occurred. The median follow up was 11 months. Conclusions: CTR is efficient for severe subglottic and upper tracheal stenosis while ECTR is efficient for subglottic stenosis extended to the glottis. Both procedures also provide a salvage therapy for patients with previous failed treatments.

[The application of thyroid alar cartilage in the reconstruction of subglottic stenosis for children].

Objective: To explore the application value of thyroid alar cartilage(TAC) in the laryngotracheal reconstruction of subglotticstenosis in the paediatric population. Methods: Twelve patients(7 males,5 females; range from 2.3 to 12.0 years) with subglotticstenosis who had undergone laryngotracheal reconstruction procedures at our hospital fromSeptember 2016 to July 2018 were analyzed retrospectively.The degree of stenosis was classified according to Myer-Cotton classification system:grade Ⅱ(n=4),grade Ⅲ(n=6) and grade Ⅳ(n=2). The stenosis planes were subglotticbut did not exceed the 3rd tracheal cartilage ring. Results: Of all 12 patients, 11 were decannulated and 1 failed. All patients with grade Ⅱ and Ⅲ patients were decannulated at one procedure. There were no severe complications such as tube dislogement,asphyxia and unhealed wound. Conclusions: The TAC for widening laryngotracheal lumen is relatively simple and reliable for laryngotracheal reconstruction in the pediatric population with subglottic stenosis. This would't cause any structural damage to the laryngeal cavity.

A new delineation method research of the clinical target volume for pancreatic cancer adjuvant radiotherapy.

PURPOSE: The purpose of this work was to establish a map model of the local recurrence location after pancreatic cancer resection and to generate a new delineation method of clinical target volume, with the aim to effectively improve the adjuvant radiotherapeutic gain ratio. METHODS AND MATERIALS: The clinical and imaging data of 48 patients with resected pancreatic head cancer and pancreatic body cancer with local recurrences were collected. Local recurrences were all plotted with reference to the geometric centre of the local recurrent foci. Based on the coordinates of the local recurrences with respect to the celiac artery or the superior mesenteric artery, a three-dimensional local recurrence map model was established on the computed tomography image. The adjuvant radiation clinical target volumes encompassing 90% of all local failures and encompassing 90% of postoperative pancreatic head cancer local failures were created respectively. This new delineation method and RTOG 0848 protocol were applied in five simulated cases, then corresponding types of target volumes and plans were generated for comparison. RESULTS: The clinical target volume encompassing 90% of all local failures was generated by expanding the combined celiac artery and superior mesenteric artery contour by 1.4cm superior, 1.9cm inferior, 2.6cm left-lateral, 3.1cm right-lateral, 1.9cm anterior and 1.6cm posterior. The corresponding expansions of clinical target volume encompassing 90% of postoperative pancreatic head cancer local failures were 1.4cm, 1.4cm, 2.1cm, 3.1cm, 1.6cm and 2.0cm. The volumes of "new" target PTV-90_edited, PTV-90_H_edited, and the standard target PTV_edited were 217.64±58.67 cm3, 207.78±50.94 cm3 and 320.72±50.94 cm3 in simulated cases. Comparison showed that the "new" target volumes were much smaller than the standard volumes per RTOG 0848 protocol, and the dose received by organs at risk was also lower in the "new" plans. CONCLUSIONS: A majority of postoperative local recurrences in patients with pancreatic head and body cancer are contained within a smaller region surrounding the celiac artery and superior mesenteric artery. The "new" volumes targeting high risk local failures may allow dose escalation and enhanced local control while minimizing radiation-related toxicity.

[Sternohyoid myocutaneous flap in pediatric laryngotracheal stenosis treatment].

Objective:To assess the indications and outcomes of laryngotracheal reconstruction (LTR) using the sternohyoid myocutaneous flap (SMF) in pediatric patients with laryngotracheal stenosis. Method:Twenty patients (15 males, 5 females; mean age, 9 years old, range 3 to 14) with laryngotracheal stenosis who underwent SMF procedures at Tangdu Hospital between August 1991 and October 2014 were analyzed. Stenosis was classified according to the Myer-Cotton grading system. Four patients were grade Ⅱ, ten were grade Ⅲ, and six were grade Ⅳ. The mean length of stenosis was 1.8 cm (rang, 0.3-4.0 cm). Three patients had concomitant unilateral vocal paralysis and 2 had bilateral vocal paralysis. Result:Fourteen of 20 patients (70%) were decannulated. The prevalence of decannulation for grade Ⅱ, Ⅲ, and Ⅳ was 100%, 70%, and 50%, respectively. There were no severe complications. Conclusion:The SMF is a relatively simple and reliable method for LTR but should be used cautiously if employed in severe cases such as grade Ⅳ with long-segment stenosis.

[Management of subglottic stenosis in children with endoscopic balloon dilation].

OBJECTIVE: To evaluate the efficacy of endoscopic balloon dilation for subglottic stenosis. METHODS: The clinical outcomes of 9 pediatric patients treated with balloon dilation were retrospectively analyzed. There were 8 male and 1 female. Their age ranged from 7 months to 7 years (mean 2.5 years). The degree of stenosis was classified according to Myer-Cotton classification as follows: grade Ⅱ (n=7) and grade Ⅲ (n=2). The causes of the stenosis were postintubation lesions (n=8) and laryngeal penetrating trauma (n=1). RESULTS: The patients had undergone 1 to 3 dilations with an average of 1.8 procedures per patient. Six (66.7%) patients were decannulated. Among them, 4(44.4%) were decannulated after one dilation procedure. Pneumothoraces occurred in 2 children postoperatively. CONCLUSION: Endoscopic balloon dilation is an effective, relatively safe and minimally invasive surgical method for patients with low-grade subglottic stenosis.

Biological mechanisms related to differences in residual feed intake in dairy cows.

Residual feed intake (RFI), defined as the difference between an animal's actual feed intake and expected feed intake over a specific period, is an inheritable character of feed conversion efficiency in dairy cows. Research has shown that a lower RFI could improve the profitability of milk production. This study explored variation in RFI by comparing the differences in body size, milk performance, feeding behavior, and serum metabolites in 29 Holstein cows in mid lactation. The cows were selected from a total of 84 animals based on their RFI following feedlot tests. Selected cows were ranked into high RFI (RFI >1 SD above the mean, n=14) and low RFI (RFI<1 SD below the mean, n=15). The low RFI cows (more efficient) consumed 1.59 kg/day less dry matter than the high RFI group (P<0.01), while they produced nearly equal 4% fat-corrected milk. The milk : feed ratio was higher for the low RFI group than for the high RFI group (P<0.05). The levels of milk protein (P<0.01), total solids (P<0.05), and nonfat solids (P<0.05) were also higher for the low RFI group, whereas milk urea nitrogen was lower (P<0.01). The daily feeding duration was shorter for the low RFI group than for the high RFI group (P<0.01). No significant differences were found in levels of glucose, ß-hydroxybutyrate, prolactin, insulin, IGF-1, growth hormone or ghrelin, but the level of neuropeptide Y was higher (P<0.01) and levels of leptin and non-esterified fatty acid (P<0.05) were lower for the low RFI group than for the high RFI group. There were substantial differences between cows with different RFI, which might affect the efficiency of milk protein metabolism and fat mobilization.

Sirolimus-Based Immunosuppressive Regimens in Renal Transplantation: A Systemic Review.

Sirolimus (SRL)-based immunosuppressive regimens have been used for preventing rejection after kidney transplantation. This review analyzes their merits and demerits compared with other conventional regimes from the aspects of acute rejection rate, graft function, as well as patient/graft survival rates. In general, SRL is mostly recommended to be used as conversion therapy from calcineurin inhibitor (CNI) after kidney transplantation in most studies. Minimization or withdrawal of cyclosporine A (CsA) could also be considered when it was combined with SRL. SRL can replace mycophenolate mofetil (MMF), and the CNI dose should be reduced appropriately in this setting. Quadruple maintenance regimens containing SRL need future study to clarify their superiority. De novo use of low-dose CNI combined with SRL has no apparent merits and thus is not recommended. De novo use of standard-dose CNI combined with SRL followed by maintenance, de novo use of CNI-free regimens, as well as SRL use in delayed graft function (DGF) patients who spare antibody induction and postpone CNI administration should also be avoided. SRL supports steroids withdrawal after kidney transplantation, and SRL combined with tacrolimus is recommended in this setting. Loading dose is recommended when initiating SRL treatment and its trough blood level should be routinely monitored.

The equipment for the preparation of micro and nanoscale metallic glassy fibers.

A supercooled liquid extraction method and apparatus for micro and nanoscale metallic glassy fiber preparation was developed. Using the fiber fabrication equipment, micro to nanoscale metallic glassy fibers with diameter ranging from 70 nm to 300 µm can be obtained by wire drawing in the supercooled liquid region of metallic glasses via superplastic deformation. The obtained metallic glassy fibers possess precisely designed and controlled sizes, high structural uniformity and high degree of surface smoothness.

Plasticity of ductile metallic glasses: a self-organized critical state.

We report a close correlation between the dynamic behavior of serrated flow and the plasticity in metallic glasses (MGs) and show that the plastic deformation of ductile MGs can evolve into a self-organized critical state characterized by the power-law distribution of shear avalanches. A stick-slip model considering the interaction of multiple shear bands is presented to reveal complex scale-free intermittent shear-band motions in ductile MGs and quantitatively reproduce the experimental observations. Our studies have implications for understanding the precise plastic deformation mechanism of MGs.

Nanoscale periodic morphologies on the fracture surface of brittle metallic glasses.

Out-of-plane, nanoscale periodic corrugations are observed in the dynamic fracture surface of brittle bulk metallic glasses with fracture toughness approaching that of silica glasses. A model based on the meniscus instability and plastic zone theory is used to explain such dynamic crack instability. The results indicate that the local softening mechanism in the fracture is an essential ingredient for controlling the formation of the unique corrugations, and might provide a new insight into the origin of fracture surface roughening in brittle materials.

Amorphous metallic plastic.

We report cerium-based bulk metallic glasses with an exceptionally low glass transition temperature Tg, similar to or lower than that of many polymers. We demonstrate that, in near-boiling water, these materials can be repeatedly shaped, and can thus be regarded as metallic plastics. Their resistance to crystallization permits extended forming times above Tg and ensures an adequate lifetime at room temperature. Such materials, combining polymerlike thermoplastic behavior with the distinctive properties of metallic glasses, are highly unusual for metallic alloys and have great potential in applications and can also facilitate studies of the supercooled liquid state.

Fracture of brittle metallic glasses: brittleness or plasticity.

We report a brittle Mg-based bulk metallic glass which approaches the ideal brittle behavior. However, a dimple structure is observed at the fracture surface by high resolution scanning electron microscopy, indicating some type of "ductile" fracture mechanism in this very brittle glass. We also show, from the available data, a clear correlation between the fracture toughness and plastic process zone size for various glasses. The results indicate that the fracture in brittle metallic glassy materials might also proceed through the local softening mechanism but at different length scales.

Human catalytic antibodies with glutathione peroxidase activity.

In order to generate catalytic antibodies with glutathione peroxidase (GPx) activity, we prepared GSH-S-DNP butyl ester and GSH-S-DNP benzyl ester as the haptens. Two ScFvs that bound specifically to the haptens were selected from the human phage-displayed antibody library. The two ScFv genes were highly homologous, consisting of 786 bps and belonging to the same VH family-DP25. In the premise of maintaining the amino acid sequence, mutated plasmids were constructed by use of the mutated primers in PCR, and they were over-expressed in E. coli. After the active site serine was converted into selenocysteine with the chemical modifying method, we obtained two human catalytic antibodies with GPx activity of 72.2U/micromol and 28.8U/micromol, respectively. With the aid of computer mimicking, it can be assumed that the antibodies can form dimers and the mutated selenocysteine residue is located in the binding site. Furthermore, the same Ping-Pong mechanism as the natural GPx was observed when the kinetic behavior of the antibody with the higher activity was studied.

[An abzyme to catalytize the deiodination of thyroxine].

AIM: To mimic an important family of selenoenzymes in organism-thyroxine (T4) deiodinases and prepare a selenium-containing abzyme catalyzing deiodination of T4. METHODS: A anti-T4 monoclonal antibody was generated by hybridoma methodology and converted into a selenium-containing abzyme by the method of chemical modification. The catalytic activity of the enzyme was measured by RIA method. RESULTS: The abzyme displayed a marked activity of catalyzing deiodination of T4 and a higher specificity to the substrate T4 than that of natural enzyme, and the double reciprocal plots of the initial rates of T3 formation vs. T4 concentration yielded a family of parallel lines. The catalytic activity could be sensitively inhibited by 6-propyl-2-thiouracil (PTU), a competitive inhibitor for dithiothreitol (DTT). CONCLUSION: An abzyme with the diodination activity was first prepared and the reaction mechanism of the enzyme was bisubstrate ping-pong one.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of phospholipase A2 and fibrinolytic enzyme, two enzymes obtained from Chinese Agkistrodon blomhoffii Ussurensis venom.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used to analyze two enzymes, phospholipase A2 and fibrinolytic enzyme isolated from Chinese Agkistrodon blomhoffii Ussurensis venom. Using sinapinic acid as the matrix, positive ion mass spectra of the enzymes were obtained. In addition to the dominant protein [M + H]+ ions, multimeric and multiply charged ions were also observed in the mass spectra. The higher the concentration of the enzymes, the more multiply charged polymer and multimeric ions were detected. Our results indicate that MALDI-TOFMS can provide a rapid and accurate method for molecular weight determination of snake venom enzymes. Mass accuracies of 0.1 and 0.3% were achieved by analysis of highly dialyzed phospholipase A2 and fibrinolytic enzyme, and these results are much better than those obtained using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. MALDI-TOFMS thus provides a reliable method to determine the purity and molecular weight of these enzymes, which are of potential use as therapeutants.