Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July 2023.Pooled standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were calculated.Sensitivity analysis,Egger’s test and Meta-regression analysis were performed for all indicators.RESULTS:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 cases.High-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and OSDI.CONCLUSION:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis

BACKGROUND No effective treatment guarantees full recovery from osteoarthritis(OA),and few therapies have disadvantages.AIM To determine if bone marrow mesenchymal stem cells(BMMSCs)and hyaluronic acid(HA)treat ankle OA in Wistar rats.METHODS BMMSCs were characterized using flow cytometry with detection of surface markers[cluster of differentiation 90(CD90),CD105,CD34,and CD45].Fifty male Wistar rats were divided into five groups of 10 rats each:Group I,saline into the right tibiotarsal joint for 2 days;Group II,monosodium iodate(MIA)into the same joint;Groups III,MIA+BMMSCs;Group IV,MIA+HA;and Group V,MIA+BMMSCs+HA.BMMSCs(1×106 cells/rat),HA(75μg/rat),and BMMSCs(1×106 cells/rat)alongside HA(75μg/rat)were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2,3,and 4 after the MIA injection.RESULTS The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4,5,and 6.Lipid peroxide significantly increased in the serum of osteoarthritic rats,whereas reduced serum glutathione and glutathione transferase levels were decreased.BMMSCs and HA significantly improved OA.The significantly elevated ankle matrix metalloproteinase 13(MMP-13)mRNA and transforming growth factor beta 1(TGF-β1)protein expression,and tumor necrosis factor alpha(TNF-α)and interleukin-17(IL-17)serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA.The effects of BMMSCs and HA on serum TNF-αand IL-17 were more potent than their combination.The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA.Additionally,BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation.CONCLUSION BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIAinduced OA.MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

Intra-articular interventions in osteoarthritis:Navigating the landscape of hyaluronic acid,mesenchymal stem cells,and plateletrich plasma

Osteoarthritis(OA)poses a substantial burden on patients,leading to pain,functional decline,and reduced quality of life.While conventional treatments focus on symptom management,disease-modifying interventions are yet to be established.This review explores the efficacy of intra-articular interventions,particularly hyaluronic acid(HA),mesenchymal stem cells(MSCs),and platelet-rich plasma(PRP),in the context of OA management.HA injections,with diverse formulations like Hylan G-F20,sodium hyaluronate,and hyaluronan,present varying outcomes,necessitating a nuanced understanding of their effectiveness and timing.MSC therapy,derived from adipose tissue,umbilical cord,or bone marrow,shows promising results in clinical improvement,with adipose-derived MSCs demonstrating efficacy in maintaining benefits over 6 mo.Conversely,bone-marrow-derived MSCs show limited effectiveness,highlighting the need for sourcespecific considerations.PRP has emerged as a superior option for long-term pain reduction and quality of life improvement,with leukocyte-poor formulations and a critical platelet count of 10 billion demonstrating optimal results.This comprehensive analysis underscores the potential of intra-articular interventions in OA management,emphasizing the need for personalized and evidence-based approaches to enhance treatment efficacy and patient outcomes.

The Value of the Measurement of Urinary Hyaluronic Acid Levels for the Diagnosis of Bladder Cancer

Objective To investigate the value of the measurement of urinary hyaluronic acid (HA) levels for the diagnosis of bladder cancer and the possibility of replacing ELISA-like assay with radioimmunoassay to detect the levels of urinary HA. Methods Using the ELISA-like assay and radioimmunoassay at the same time to measure the HA levels in the urine specimens from 49 bladder cancer patients, 12 benign bladder tumor patients, 30 other genitourinary disease patients and 20 normal controls. Results There is not much difference between the consequences of the urinary HA levels whether we used the ELISA-like assay or radioimmunoassay to detect every specimen (P>0.05). When we used the results with radioimmunoassay for analysis, we found the levels of urinary HA of bladder cancer patients were 2–4 times than those of the benign bladder tumor patients, other genitourinary disease patients or normal individuals (P<0.01); With 137.5 ngHA/mg protein (113.6±23.9 ng/mg) as a minimum cutoff limit, this assay had a good sensitivity (91.8%) and specificity (91.9%) for the diagnosis of bladder cancer. Its difference in sensitivity meant a lot when compared with urine cytology (48.9%,P<0.01). Conclusion The urinary HA assay is a simple, convenient, noninvasive credible and cheap method with satisfactory sensitivity and specificity for the diagnosis of bladder carcinoma; radioimmunoassay is also a good means to measure the urinary HA levels. Key words Bladder carcinoma - Hyaluronic acid - Urine

Influence of BOL on hyaluronic acid,laminin and hyperplasia in hepatofibrotic rats

AIM: To study the anti-hepatofibrosis mechanism of Bie Jia Jian oral liquid (BOL). METHODS: The model was induced by subcutaneous injection of CCl(4). BOL was administered and the change of serum hyaluronic acid (HA) and laminin (LN) was observed and the degeneration of liver cells and the degree of fibre hyperplasia analyzed. Changes of ultra micro-structure in liver cells were observed in some samples. RESULTS: HA was reduced in both the groups with low and high dosage of BOL, which showed a remarkable difference as compared with that of the model group (low dosage group: 376.15 microg/L+/-35.48 microg/L vs 806.07 microg/L+/-98.49 microg/L P【0.05; high dosage group: 340.14 microg/L+/-30.18 microg/L vs 806.07 microg/L+/-98.49 microg/L P【0.05). The LN content of low and high dosage group of BOL was lower than that of model group (low dosage group: 71.99 microg/L+/-8.15 microg/L vs 133.94 microg/L+/-14.45 microg/L P 【0.01; high dosage group: 71.68 microg/L+/-11.62 microg/L vs 133.94 microg/L+/-14.45 microg/L P【0.01) and colchicine group (low dosage group: 71.99 microg/L+/-8.15 microg/L vs 118.28 microg/L+/-16.13 microg/L P 【 0.05; high dosage group: 71.68 microg/L+/-11.62 microg/L vs 118.28 microg/L+/-16.13 microg/L P 【0.05). Examined by Ridit, BOL could reduce the degeneration and necrosis of liver cells (chi(2)=11.99 P【0.05), the degree of fibre hyperplasia (chi(2)=13.24 P【0.05) and the pathological change of ultra micro-structure as well. CONCLUSION: The BOL has certain therapeutic effect on the experiment hepatofibrosis. Its mechanisms might include: protecting the function of liver cells, inhibiting excessive synthesis and secretion of extracellular matrix from hepatic stellate cells, relieving the capillarization of hepatic sinusoid, improving liver micro-circulation, and regulating immune function.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

Serum hyaluronic acid, procollagen type Ⅲ and Ⅳ in histological diagnosis of liver fibrosis

OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.

SERUM CONCENTRATIONS OF HYALURONIC ACID, PROCOLLAGEN TYPE III NH_2-TERMINAL PEPTIDE, AND LAMININ IN PATIENTS WITH CHRONIC CONGESTIVE HEART FAILURE

Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.

3D bioprinted hyaluronic acid‑based cell‑laden scaffold for brain microenvironment simulation

Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.

Crosslinked hyaluronic acid with liposomes and crocin for management symptoms of dry eye disease caused by moderate meibomian gland dysfunction

AIM:To study the effect of uncrosslinked and crosslinked hyaluronic acid combined with other artificial tear components in patients with dry eye caused by moderate meibomian gland dysfunction.METHODS:Prospective,single-blind,contralateral eye study.Fifty eyes(25 patients)were analyzed.Eye selection for each tear type was random,and the eye drop formulations,0.4%uncrosslinked hyaluronic acid and 0.2%galactoxyloglucan(tear A)and 0.15%crosslinked hyaluronic acid,crocin,and liposomes(tear B)were used.The determined dosing schedule was three times a day for six weeks,and the study participants underwent a clinical examination before and 45 d after lubricant treatment.The Schirmer test,tear breakup time(TBUT)test,and Ocular Surface Disease Index(OSDI)questionnaire were applied before and after instillation period with both types of artificial tears.RESULTS:On the Schirmer test,a significant improvement was obtained with both tear A(P<0.01)and tear B(P<0.01).On the TBUT test,a significant improvement was obtained with tear A(P<0.01)and tear B(P<0.01).The OSDI score significantly decreased after instillation period with both artificial tear types(P<0.01).CONCLUSION:Uncrosslinked hyaluronic acid combined with other components,such as tamarind seed polysaccharide,and crosslinked hyaluronic acid combined with liposomes and crocin are effective for management symptoms of dry eye disease.

Oral absorption of hyaluronic acid and phospholipids complexes in rats

AIM： To prepare a complex of hyaluronic acid （HA） and phospholipids （PL）, and study the improvement effect of PL on the oral absorption of HA. METHODS： The complex of HA-PL （named Haplex） was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry （DSC）. The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly： （1） a normal saline （NS） control group; （2） an HA group; （3） a mixture group and （4） a Haplex group. After intragastric administration, the concentration of HA in serum was determined. RESULTS： The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h （P 〈 0.05）. The AAUCo-12, of Haplex was also greater than that of the other three groups （P 〈 0.05）. CONCLUSION： The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.

No difference in high-magnification morphology and hyaluronic acid binding in the selection of euploid spermatozoa with intact DNA

In this study, we compared conventional sperm selection with high-magnification morphology based on the motile sperm organellar morphology examination （MSOME） criteria, and hyaluronic acid （HA） binding for sperm chromosome aneuploidy and DNA fragmentation rates. Semen from 50 severe male factor cases was processed through density gradient centrifugation, and subjected to sperm selection by using the conventional method （control）, high magnification at x6650 or HA binding. Aneuploidy was detected by fluorescence in situ hybridization with probes for chromosomes 13, 18, 21, X and Y, and DNA fragmentation by the terminal deoxynucleotidyl transferase dUTP nick end labelling （TUNEL） method. Spermatozoa selected under high-magnification had a lower DNA fragmentation rate （2.6% vs. 1.7%; P=0.032）, with no significant difference in aneuploidy rate （0.8% vs0.7%; P=0.583）, than those selected by the HA binding method. Spermatozoa selected by both methods had much lower aneuploidy and DNA fragmentation rate than the controls （7% aneuploidy and 26.8% DNA fragmentation rates, respectively）. In the high-magnification group, the aneuploidy rate was lower when the best spermatozoa were selected than when only the second-best spermatozoa were available for selection, but the DNA fragmentation rate was not different. In conclusion, sperm selection under high magnification was more effective than under HA binding in selecting spermatozoa with low DNA fragmentation rate, but the small difference （0.9%） might not be clinically meaningful. Both methods were better than the conventional method of sperm selection.

Determination of sodium hyaluronate in pharmaceutical formulations by HPLC–UV

A liquid chromatography （HPLC） method with UV detection was developed for determination of sodium hyaluronate in pharmaceutical formulation. Sodium hyaluronate is a polymer of disaccharides, composed of D-glucuronic acid and D-N-acetylglucosamine, linked via alternating 13-1, 4 and D-l, 3 glycosidic bonds. Being a polymer compound it lacks a UV absorbing chromophore. In the absence of a UV absorbing chromophore and highly polar nature of compound, the analysis becomes a major challenge. To overcome these problems a novel method for the determination of sodium hyaluronate was developed and validated based on size exclusion liquid chromatography （SEC） with UV detection. An isocratic mobile phase consisting of buffer 0.05 M potassium dihydrogen phosphate, pH adjusted to 7.0 using potassium hydroxide （10%） was used. Chromatography was carried out at 25 ~C on a BioSep SEC $2000, 300 mm ~ 7.8 mm column. The detection was carded out using variable wavelength UV-vis detector set at 205 nm. The compounds were eluted isocratically at a steady flow rate of 1.0 mL/min. Sodium hyaluronate retention time was about 4.9 min with an asymmetry factor of 1.93. A calibration curve was obtained from 1 to 38 g/mL （r〉0.9998）. Within-day % RSD was 1.0 and between-day % RSD was 1.10. Specificity/selectivity experiments revealed the absence of interference from excipients, recovery from spiked samples for sodium hyaluronate was 99-102. The developed method was applied to the determination of sodium hyaluronate in pharmaceutical drug substance and product.

Preparation and Identification of Hyaluronic Acid From Fresh Pigskin

Hyaluronic acid （HA） had been prepared from pigskin residues with neutral proteinase. The preparing results and conditions were studied. After extracting and purification, HA was detected through ultraviolet spectra and infraction spectrum, and its content and purity were tested by carbazole and Elason-Morgan, respectively. This results indicated that significant quantities of HA could be prepared in fresh pigskin with biologic enzyme, and the pure HA was cosmetic grade and food grade.

Adjunctive platelet-rich plasma and hyaluronic acid injection after arthroscopic debridement in Kellgren-Lawrence grade 3 and 4 knee osteoarthritis

BACKGROUND Osteoarthritis(OA)is the most common cause of pain and disability,predominantly affecting the knee.The current management of knee OA falls short of completely stopping disease progression,particularly in Kellgren-Lawrence(KL)grade 3 and 4 knee OA.As such,joint replacement is often recommended,although only 15%-33%of candidates accept it.Alternative therapeutic options are still needed to prevent the progression of joint damage and delay the need for knee arthroplasty.AIM To investigate the effect of adjunctive platelet rich plasma(PRP)and hyaluronic acid(HA)after arthroscopic debridement in KL grade 3 and 4 knee OA.METHODS This retrospective cohort study used the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score and WOMAC sub-scores(pain,stiffness,and function)to assess 21 patients,grouped according to medical record data of treatment received:Arthroscopic debridement(n=7);arthroscopic debridement with PRP(n=7);or arthroscopic debridement with HA(n=7).WOMAC scores and sub-scores at baseline and at 3 mo and 5 mo posttreatment were recorded.The three-group data were statistically analyzed using the tests of paired t,one-way analysis of variance,and post hoc least significant difference.RESULTS All three treatment groups showed significant improvements in WOMAC score and sub-scores from before treatment to 3 mo and 5 mo after treatment.However,the arthroscopic debridement with PRP treatment group,in particular,showed a significantly lower WOMAC pain score than the group who received arthroscopic debridement alone at 5 mo after the procedure(P=0.03).CONCLUSION Compared to arthroscopic debridement alone,adjunctive PRP after arthroscopic debridement significantly lessened the patients’pain symptom.

Correlation Between Hyaluronic Acid,Hyaluronic Acid Synthase And Human Renal Clear Cell Carcinoma

Objective：To study the correlation between hyaluronic acid（HA）,hyaluronic acid synthase（HAS） and human renal clear cell carcinoma（RCCC）.Methods：The expression of three HAS isoforms＇ gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results：All RCCC and adjacent normal tissues expressed three HASs＇ mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant（all P values 0.05）;but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms＇ mRNA in RCCC tissues were increased evidently and their differences were significant（all P values 0.0001）;but at the protein level,only the expression of HAS3 increased evidently（P=0.022）.In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases（16/93） presented weakly positive HA staining in few cancer nests（5%-30%）,the difference were significant（P0.0001）.In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs＇ mRNA protein differential expression all had no statistical significance（all P values 0.05）.Conclusion：Different from other malignancy,HA and HASs（except for HAS3） may not play important roles in the biological progress of human RCCC.

Preparation and Kinetics of a Novel Glutathione Peroxidase Mimic——Selenium-modified Hyaluronic Acid

A selenium-modified hyaluronic acid（HA） compound（SeHA） was synthesized as a mimic of glutathione peroxidase（GPX）. IR and NMR spectra of SeHA predict that the --CH2OH group of the N-acetyl-D-glucosamine in HA was modified by group --Sell. There are averagely 152 --Sell groups in one SeHA molecule. The GPX activities are 103.88, 32. 15 and 152. 71 U/μmol, respectively, when the substrates were H2O2, BuOOH and CuOOH. Ping-pong mechanism was observed in the steady-state kinetic studies of the reactive oxygen species（ROS） consuming reaction. Result of reactions of SeHA with free radical capturer 2,6-di-tert-butyl-4-methylphenol（BHT） shows that the catalysis is based on a non-free radical-mechanism and the SeHA can not be inhibited by iodoacetate, an enzyme inhibitor.

Role of artificial tears with and without hyaluronic acid in controlling ocular discomfort following PRK: a randomized clinical trial

AIM:To compare outcomes of applying preservative free artificial tears(PFAT)with and without hyaluronic acid(HA)in early postoperative course following photorefractive keratectomy(PRK).METHODS:In this triple-blinded randomized clinical trial,PRK procedure was performed on both eyes of 230 patients.Following PRK,patients were divided into three groups:the HA^(+)group,44 patients PFAT containing HA;the HA-group,71 patients PFAT without HA were administered 5 times per day(every 4 h);the third group,115 patients received no PFAT before lens removal.On the 1st and 4th postoperative day,Visual Analogue Score(VAS)was utilized to evaluate patient’s level of pain.Participants were asked to complete a questionnaire about the severity of eye discomfort ranked from 0 to 10(0=no complaint;10=most severe complaint experienced).RESULTS:In eyes receiving PFAT with or without HA(Drop group),mean scores for epiphora,foreign body sensation,and blurred vision on the 1st postoperative day were statistically lower(P<0.05).Filamentous keratitis(FK)was detected in 11(4.7%)eyes,and recurrent corneal erosion(RCE)was observed in 5(2.1%)eyes.In the control group,FK was noted in 16(6.9%)eyes while 13(5.6%)eyes had RCE and 5(2.1%)eyes had corneal haze.The rate of complications was statistically lower in Drop group(P=0.009).However,the aforementioned scores were not statically different between HA^(+)and HA-group one and two(P=0.29).CONCLUSION:Following PRK,applying PFAT with and without HA yields faster visual recovery,decreases postoperative ocular discomfor t and haze formation;however there is no additive effect for HA.

Rheological and Biological Characteristics of Hyalu-ronic Acid Derivative Modified by Polyethylene Glycol

Hyaluronic acid （HA） was chemically modified by polyethylene glycol. Meanwhile, the dynamic mechanics properties of HA derivative and its viscoelastic changes were measured on 3ARES3 Rheometer （Japan） at 25℃. Dried cross-linked films of 10- 10 mm^2 were immersed in phosphate buffered saline（PBS： pH 7.4） at 37 ℃ with different time periods to measure its water content and in vitro degradation. Moreover, cell cultured solutions, which were in the different cultivation vesse with 1 mg/mL Solution of HA derivative as doing experimental sample for 2 d, 4 d and 7 d, were observed, respectively, by an inverted discrepancy microscope. The cell relative growth rate was analyzed with the SPSS10.0 mathematic statistic software. Based on the above experiments, structure-modified HA derivative can meet the requirements of biomaterials in view of rheological and degradation in vitro and cytotoxicity charactereistics from clinical medical aspect under this experiment conditions.