Clinical efficacy of intra-articular parecoxib injection for the treatment of early knee osteoarthritis / 中国骨伤

OBJECTIVE@#To observe and evaluate the clinical effect of intra-articular injection of parecoxib in patients with early knee osteoarthritis.@*METHODS@#From September 2016 to August 2017, 107 patients with early knee osteoarthritis were treated, including 50 males and 57 females, aged 45 to 64 (51.9±4.2) years. They were divided into basic therapy+oral glucosamine group(group A) 36 cases, oral celecoxib+basic therapy+oral glucosamine group(group B) 36 cases, intra-articular injection of parecoxib+basic therapy+oral glucosamine group(group C) 35 cases. There was no significant difference in gender, age, BMI and clinical stage(Kellgren-Lawrence classification) between the three groups before treatment. VAS score, HSS score and patient satisfaction were compared before and after treatment in the three groups. The levels of inflammatory cytokines in synovial fluid were measured before and after treatment in the three groups.@*RESULTS@#All cases were followed up for(15.2±2.6) months on average. The VAS score and HSS score of each group were improved after treatment(<0.001). There were significant differences in VAS and HSS scores among the three groups after treatment(<0.001). The clinical efficacy of group C was better than that of group A and B(<0.001), group B was better than that of group A(<0.001), and group C had the highest satisfaction(<0.001). After treatment, the concentration of proinflammatory factor TNF-α and IL-6 in the synovial fluid of each group decreased(<0.001) and the concentration of anti-inflammatory factor IL-10 increased(<0.001). After treatment, the concentrations of TNF-α, IL-6 and IL-10 in the synovial fluid of the three groups were significantly different(<0.001).@*CONCLUSIONS@#For patients with early knee osteoarthritis, intra-articular injection of parecoxib can significantly improve clinical symptoms and avoid adverse reactions of long-term oral NSAIDs, which is an effective treatment.

Comparison of efficacy of first-line administration of generic dasatinib or imatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia treated by hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+) ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph(+) ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph(+) ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ(2)=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ(2)=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ(2)=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ(2)=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions: First-line administration of generic dasatinib could improve EFS for Ph(+)ALL patients treated by HSCT when compered with imatinib.

Expression of PDCD5 and caspase 3 in the cochlea of different age of C57BL/6J mice / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the age related changes of the expression of programmed cell death 5 (PDCD5) and caspase 3 in the cochlea of the different age of C57BL/6J mice. The relationship of PDCD5 and caspase 3 and the possible roles in the pathogenesis of presbycusis were also discussed.</p><p><b>METHODS</b>C57 mice of 3, 6, 9 and 12 months old were selected and divided into 4 groups, with 15 mice in each group. Auditory function of C57BL/6J mice was measured by auditory brainstem response (ABR) respectively. The changes of PDCD5 and Caspase 3 protein in the cochlea were detected by immunohistochemistry and Western blotting, the changes of PDCD5 mRNA and caspase 3 mRNA were detected using RT-PCR.</p><p><b>RESULTS</b>With the increase of age, the mean value for ABR thresholds in response to click, 4 kHz and 8 kHz sound stimulus of C57 mice gradually increased, the expression of PDCD5 and caspase 3 were increased also. At 3 months and 6 months of age in the cochlea of C57, all sorts of expression of PDCD5 and caspase 3 and the expression were enhanced with age. There was an evident expression at 9 months age, but the highest expression was detected at 12 months age. The PDCD5 and Caspase 3 expression were statistically different in each group (P < 0.05). The changes of PDCD5 and caspase 3 mRNA expression were in accordance with that of PDCD5 and Caspase 3 protein expression by the real-time PCR.</p><p><b>CONCLUSIONS</b>The expression levels of PDCD5 and caspase 3 in the cochlea of C57 mice increase with age, the results suggested that the expression of PDCD5 and caspase 3 might play an important role in the pathogenic mechanism of presbycusis.</p>

A pilot investigation on serum protein fingerprinting of nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To establish a preliminary foundation for developing a serum proteomics diagnostic model of nasopharyngeal carcinoma (NPC) by comparing the differences in serum protein fingerprints between patients with NPC and healthy subjects and between different types of NPC.</p><p><b>METHODS</b>The serum samples of 41 patients with different types of NPC and 20 healthy subjects were collected. Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used to detect the blood samples to obtain serum protein mass spectrum, i.e. serum protein fingerprinting. Biomarker Wizard and Biomarker Patterns system software were used to compare the differences in serum protein mass spectrum between NPC patients and healthy subjects and between different types of NPC, and to screen out the NPC-related serum proteins.</p><p><b>RESULTS</b>Compared with the healthy control, NPC patients emerged 9 very prominent protein peaks (P < 0.001), with the combined differential peaks. No significant difference was found in relative amount of serum proteins with different molecular mass between different types of NPC (P > 0.05).</p><p><b>CONCLUSIONS</b>The serum marker proteins and specific protein fingerprints of NPC can be screened out by SELDI-TOF-MS, which could be used to develop a serum proteomics model for clinical screening and early diagnosis of NPC.</p>

Rapid cochlea lesion induced by co-administration of kanamycin and furosemide in mouse / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the ototoxicity of co-administration of kanamycin and furosemide in mouse and establish a reliable model to induce a sensorineural hearing loss.</p><p><b>METHODS</b>CBA/J mice strain was selected, with the age around 3-4 weeks old, to be received a single subcutaneous injection of kanamycin at dose of 1 g/kg and another single intraperitoneal injection of furosemide at dose of 0.4 g/kg 30 - 45 min afterward. The auditory brainstem response (ABR) threshold shift was tested. The series of experimental methods including propidium iodide, phalloidin staining, semithin section toluidine blue staining, TUNEL, scanning electron microscopy and transmission electron microscopy were applied to observe the characteristics of the lesion of cochlea and hair cells. The time course was set as following: before injection, 12, 24, 48 hours and 1, 2, 4, 12 weeks after injections, respectively.</p><p><b>RESULTS</b>The ABR threshold shift was firstly presented a significant increase at 12 h after injection at 2, 4, 8 kHz, then the ABR threshold kept going up during next 36 h until it was presented a stable level around 90 dB. Pathological examination showed an absence of outer hair cells at basal turn rapidly since 12 h after treatment, and then by 48 h the most commonly observed lesion, where all outer hair cells throughout the length of the cochlea were killed, in the contrast, however, the inner hair cells loss were delayed and mild. TUNEL-positive nuclei demonstrated that most hair cells died via an apoptotic pathway. In scanning electron microscopy abundance of necrotic outer hair cells were detected by 24 h after treatment, in which reticular lamina were collapsed. Then all outer hair cells were replaced by expansion of heads of supporting cells. At 48 h after treatment, marginal cells presented a swollen and some of them were observed to be fused. In addition, spherical cell extrusion appeared to leak out from some marginal cells. By 2 weeks, nearly all microvillus were lost and marginal cells presented a shape of stone-like change. A significant and progressive decrease in strial vascularis thickness was found, of which the reason probably related with a reduction in volume of marginal cells.</p><p><b>CONCLUSION</b>This systemic protocol eliminates hair cells extensively in vivo, and it could be a reliable model to examine different aspects of cochlear pathology in transgenic or mutant mice strains.</p>

A novel retractor designed for mouse microsurgery / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To introduce a novel retractor with magnetic fixator for mouse microsurgery.</p><p><b>METHODS</b>The retractor was consisted of a magnet, a screw, two screw nuts and a hook made of dental stainless wire. The screw was connected to the magnet with magnetic force, and then was assembled to be a so-called magnetic fixator. The hook was clamped by two screw nuts on the screw, and these makes up of the retractor finally. Comparison has been done between the novel retractor and traditional retractor in the clinical application of the otocyst exposure.</p><p><b>RESULTS</b>The retractor can quickly claw and retract massive tissue like muscles and vessels to the target position, thus, this properties would tend to offer a clear and expanded operative field. In addition, the height, orientation and strength of traction was all adjustable. By Comparison with tradition retractor, the operative incision can be shorten via the application of the retractor, also, it would reduce the trauma of muscles and vessels as well as the accidental rate of bleeding in the process of operation.</p><p><b>CONCLUSIONS</b>The retractor can offer a expanded operative field of the mouse otocyst conveniently. It could be a simple, powerful and minimal invasive tool for mouse microsurgery.</p>

Association of age-related hearing loss with mice which expressed only one copy of gene encoding NKCC1 co-transporter / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To generate transgenic mice of NKCC1 +/- (heterozygous) and NKCC1 +/+ (wild-type) that have a targeted disruption in the NKCC1 gene in order to investigate the relationship of one copy of NKCC1 gene (NKCC1 +/-) and age-related hearing loss (AHL) and to study the possible pathogenesis of AHL METHODS: Auditory function of NKCC1 +/- mice was detected regularly by auditory brain response (ABR) and endocochlear potential (EP). Morphology of cochlea was observed by scanning electron microscope and content of NKCC1 protein was detected by Western blot.</p><p><b>RESULTS</b>The mean value for ABR thresholds was elevated in NKCC1 +/- mice more than that of NKCC1 +/+ mice (P < 0.01). A progression of age-related hearing loss was found in NKCC1 +/- mice. Compared with younger NKCC1 +/- mice, the mean value for ABR thresholds in aged NKCC1 +/- mice was significantly increased (P < 0.05). The EP of NKCC1 +/- aged mice was also significantly decreased more than that of the younger NKCC1 +/+ mice (P < 0.05). And content of NKCC1 protein were reduced with the growth of the age. The scanning electron microscope showed a kind of scattered punctiform absence of outer hair cells in elder NKCC1 +/- mice cochlea.</p><p><b>CONCLUSIONS</b>NKCC1 gene maybe takes part in the pathogenesis of AHL. Mice that expressed only one copy of NKCC1 could lead to AHL. AHL may be correlative with the amounts of NKCC1 protein and its function and also with the loss of outer hair cells perhaps.</p>

Role of ion channel Na-K-2Cl and alpha2 Na, K-ATPase in cochlear potassium cycling and auditory function / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the auditory function and the role of NKCC1 and alpha2 Na, K-ATPase in the potassium recycling of cochlea.</p><p><b>METHODS</b>NKCC1(+/-) / alpha2 Na, K-ATPase(+/-) mice model was established from NKCC1(+/-) and alpha2 Na, K-ATPase(+/-) mice. The auditory function of all strain mice were detected by auditory brainstem response (ABR) and endocochlear potential (EP) to investigate the role of NKCC1 and alpha2 Na, K-ATPase in the potassium recycling of cochlea. Furosemide and ouabain were applied to block the two channels in Castel mice line which can long-time maintain normal auditory function and then their auditory function was detected by ABR to authenticate the mode of potassium recycling in vivo and the relationship between cochlear potassium recycling and NKCC1(+/-) and alpha2 Na, K-ATPase.</p><p><b>RESULTS</b>The mean value for ABR thresholds in response to stimulus was elevated in NKCC1(+/-) and alpha2 Na, K-ATPase (+/-) mice [(38.49 +/- 12.29) dB and (53.32 +/- 7.62) dB) ] respectively, which was significantly increased compared with that observed in wild type mice [(23.13 +/- 3.78) dB, P < 0.05) ]; The EP value of NKCC1(+/-) [(78 +/- 7) mV] and alpha2 Na, K-ATPase(+/-) mice [(71 +/- 14) mV] was decreased compared with that of NKCC1(+/-) / alpha2 Na, K-ATPase(+/-) mice [( 86 +/- 11) mV]. The auditory function of NKCC1(+/-) / alpha2 Na, K-ATPase(+/-) mice could simulate the model of cochlear potassium recycling well. NKCC1 and Na, K-ATPase were great of importance in the potassium recycling, while the two ion channels were in restrict dynamic equilibrium. Castel mice line after administration with furosemide developed significant ABR threshold shifts (P < 0.05) compared with control group. Castel mice line after administration with ouabain also developed greatly significant ABR threshold shifts (P < 0.05) compared with control group. ABR threshold shifts in mice after administration both furosemide and ouabain was attenuated compared with only administration with furosemide (P < 0.01).</p><p><b>CONCLUSIONS</b>Ion channel NKCC1 and alpha2 Na, K-ATPase played important roles in the inner ear potassium recycling. Dysfunction of either of them could influence potassium concentration in the endolymph and lead to hearing loss subsequently. The role of NKCC1 and alpha2 Na, K-ATPase in cochlear potassium recycling was authenticated in vivo. The two ion channels contribute the key role for dynamic equilibrium in cochlear potassium recycling and are of great importance for the metabolism of potassium in the inner ear to maintain the normal auditory function.</p>

Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>After establishing a murine model of aminoglycoside antibiotic (AmAn) induced ototoxicity, the sensitivity of AmAn induced ototoxicity in three murine strains and the effect of kanamycin on the expression of Na-K-2Cl cotransporter-1 (NKCC1) in stria vascularis were investigated.</p><p><b>METHODS</b>C57BL/6J, CBA/CaJ, NKCC1(+/-) mice (24 of each strain) were randomly divided into four experimental groups: A: kanamycin alone; B: kanamycin plus 2, 3-dihydroxybenzoate; C: 2, 3-dihydroxybenzoate alone; and D: control group. Mice were injected with kanamycin or/and 2, 3-dihydroxybenzoate twice daily for 14 days. Auditory brainstem response (ABR) was measured and morphology of cochlea delineated with succinate dehydrogenase staining. Expression of NKCC1 in stria vascularis was detected immunohistochemically.</p><p><b>RESULTS</b>All three strains in groups A and B developed significant ABR threshold shifts (P < 0.01), which were accompanied by outer hair cell loss. NKCC1 expression in stria vascularis was the weakest in group A (A cf D, P < 0.01) and the strongest in groups C and D (P < 0.05). CBA/CaJ mice had the highest sensitivity to AmAn.</p><p><b>CONCLUSIONS</b>Administration of kanamycin established AmAn induced ototoxicity. Kanamycin inhibited the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate attenuated AmAn induced ototoxicity-possibly by enhancing the expression of NKCC1. Age related hearing loss did not show additional sensitivity to AmAn induced ototoxicity in murine model.</p>