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.

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.

Hyaluronic acid injection in the auricular base for the aesthetic correction of lying ears:A retrospective study

Background Ears play an important role in facial profiles.Lying ears are not perceived favorably in Asian cultures;therefore,surgical procedures are implemented to adjust this defect.However,surgery has complications and requires recovery time.We introduced a hyaluronic acid(HA)injection technique to aesthetically improve ear prominence.Methods This retrospective study examined 25 Chinese patients aged 20-47 years with congenital lying ears who received HA injections in the auricular base at Shanghai Ninth People’s Hospital and Hangzhou Yijie Medical Cosmetology Clinic between November 2019 and December 2022.The average injection volume was 6.32±1.22 mL in the auricular base unilaterally,and the follow-up time ranged from 6 to 24 months.Morphological measurement data were recorded.Two-dimensional(2D)and three-dimensional(3D)images were obtained to evaluate the effects.Results All patients showed improvements in ear prominence.The cranioauricular angle(CAA)increased from 22.24°±4.53°to 65.90°±5.38°immediately post-injection and was maintained at 49.18°±4.74°6 months later.The ear projection(EP)increased from 14.75±2.72 mm to 26.26±2.94 mm immediately post-injection and was 22.51±2.68 mm after 6 months.No serious complications were noted.Conclusion HA injection in the auricular base effectively corrected the lying ears and aesthetically optimized the facial profile.It also had a face-lift effect that made the face look younger and more compact.The injection procedure was minimally invasive and required no recovery period.The effect was maintained for a long time and was satisfactory.

Development of hyaluronic acid-based edible film for alleviating dry mouth

For alleviating dry mouth symptoms,edible films based on hyaluronic acid(HA)with 3 different m(800,1200 and 2300 kDa)were prepared(800 F,1200 F and 2300 F,respectively),and the properties as well as effectiveness were compared.The concentration of each HA dispersion for film forming was set as 3.0%,1.5%or 1.0%,for the m800,1200 and 2300 kDa,respectively,based on the solubility.The 800 F showed the highest thickness,tensile strength,and water vapor transparency,whereas obtained the lowest transparency and elongation at break among samples.All of the HA films showed safety against microorganism during 28 storage day at 40℃with 60%humidity.The optimum site for film attachment in mouth was the palate,and800 F was the most effective for stimulating saliva secretion,eliciting a 38%increase compared to control(without film),tested by the elderly over 65 years old.By the sensory test,800 F was also the most acceptable.Based on above results,the edible films effectively stimulating saliva secretion could be produced with HA,and the physical,sensory characteristics as well as disintegration times of the film could be controlled by mand the dissolution concentration of HA.

Design of Novel Wound Dressing Composed of Collagen and Hyaluronic Acid Containing Epidermal Growth Factor

This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.

Preparation and characterization of nanoparticles from quaternized cyclodextrin-grafted chitosan associated with hyaluronic acid for cosmetics

Hyaluronic acid(HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin and, thus, limits its benefits to topical effects. Thus, the objective of this study is to prepare nanoparticles of quaternized cyclodextrin-grafted chitosan(QCD-g-CS) associated with HA in different molar ratios of QCD-g-CS and HA. The conjugation of the carboxylic moieties of HA and the amides of QCD-g-CS was confirmed by Fourier-transform infrared spectroscopy. Thus, the system was optimized to create nanoparticles with a small size(235.63 ± 21.89 nm), narrow polydispersity index(0.13 ± 0.02), and zeta potential of 16.07 ± 0.65 m V. The association efficiency and loading efficiency were determined by ultra-performance liquid chromatography as 86.77 ± 0.69% and 10.85 ± 0.09%, respectively. The spherical morphology of the obtained nanoparticles was confirmed by transmission electron microscopy. Moreover, the in-vitro hydrating ability was significantly higher( P < 0.001) than that of bulk HA(3.29 ± 0.41 and 1.71 ± 0.05 g water/g sample, respectively). The safety of these nanoparticles at concentrations in the range of 0.01–0.10 mg/ml was confirmed via tests on human skin fibroblasts. Together, these results demonstrate that the developed nanoparticles are promising for future applications in cosmetics.

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.

Synthesis and Kinetics of a Novel Mimic with Glutathione Peroxidase Activity—Tellurium-containing Hyaluronic Acid (TeHA)

A novel mimic was synthesized by modifying hyaluronic acid （HA） with tellurium, whose function is similar to that of glutathione peroxidase （GPX）. The structure of TeHA was characterized by means of IR and NMR, the target-Te was located at -CH2OH of the N-acetyl-D- glucosamine of HA. The H202 reducing activity of TeHA, by glutathione （GSH）, was 163.6 U/μmol according to Wilson＇s method. In contrast to other mimics, TeHA displayed the highest activity. Moreover, TeHA accepted many hydroperoxides as its substrates, such as H2O2, cumenyl hydroperoxide （CuOOH） and tert-butyl hydroperoxide （t-BuOOH）, and CuOOH was the optimal substrate of TeHA. A ping-pong mechanism was observed in the steady-state kinetic studies of the reactions catalyzed by TeHA.

Use of High-Resolution Ultrasound (HRU) in the Assessment of Deep Injections of CHAP-Hyaluronic Acid (CHAP-HA) Fillers for Midface Lift

High-resolution ultrasound (HRU) imaging is a useful tool to study hyaluronic acid (HA) filler injection in the face. It is noninvasive, quick, well-tolerated, and can provide in vivo and dynamic information. The formations of pools or pearls in HA fillers could be observed real time during injection. The plane of injection could be determined accurately, and there were no specimen manipulation artifacts. It was observed that HA gel fillers with differing production technologies showed distinct spread and distribution patterns in the periocular tissues on HRU examination. The authors used HRU to assess deep injections of CHAP-Hyaluronic Acid (CHAP-HA) fillers for midface lift. 10 patients who underwent bilateral midface deep injections using CHAP-HA filler were examined with HRU before and immediately after treatment, and in 2 weeks and one month later. The CHAP-HA appeared as hypoechoic densities within the preperiosteal plane in HRU. CHAP-HA adopted variable morphology within the tissue depending on individual tissue densities and the compliance of the tissues in the plane of injection. CHAP-HA was unidentifiable with surrounding tissue after one month in 13 of the 20 injection sites. HRU allows in vivo study of CHAP-HA injection behavior and could be a tool for further studies of HA-tissue reactions.

Characteristics of Hyaluronic Acid Derivative Cross-linked by Polyethylene Glycol

Characteristic and dynamic viscosities of Hyaluronic acid （ HA ） derivative modified by polyethylene glycol （PEG） were tested with different reaction times （6 h,12 h,18 h and 24 h ）, different molar ratio of HA/PEG （1/10,1/5,1/3 and 1/2）, different molecular weight of PEG（400,6 000 and 20 000） and mass fraction is 0. 4% by Wushi Viscosimeter and L-90 Rheometer at 25℃ . Characteristic viscosity of HA derivative had the largest value in 12 h, which decreased with increasing of PEG molecular weight, bat its aqueous dynamic viscosity increased with increment of PEG molecular weight. Meanwhile, we tested dynamic mechanic properties of HA derivative by 3ARES3 Rheometer at 25℃ to study viscoelastic changes and to compare change difference from viscosity to elasticity with the changes of vibration frequency between unmodified HA and HA derivative. Change from low vibrated freqnency to high one of solution resulted in change from viscosity to elasticity of solution. In conclusion, as to the rheological properties, structure- modified HA derivative meets the requirement of biomaterial .

Enhancement of Periodontal Healing by Application of a Novel Ointment Compared with Hyaluronic Acid, Histological Observation in Animal Model

Objectives:?The early healing of the periodontal wound in oral cavity may be critical to the treatment outcome. Thus, we made a novel ointment based on natural constituents that our recent investigation suggested a positive therapeutic effects on gingival wounds. The present study was conducted to evaluate the role of this novel biomaterial on periodontal wound healing including soft as well as hard tissue. Materials and Methods: Experimental periodontitis was induced by wire tied around the cement-enamel junction of I2, P1, P3?and M1?in six adult, healthy beagle dogs. After 3 months, mucoperiostal flap elevated and root surfaced was thoroughly scaled and planed. Randomly, three materials including our ointment with two different ratios including materials A and B and hyluronic acid were applied topically and then the flaps were repositioned and sutured. Three dogs at day 7 and the three remaining ones two weeks post-surgery were sacrificed and histological changes were monitored. Results: The result of this study showed that the local applications of this novel ointment promoted the healing process particularly fibroblast proliferation and collagen density remarkably in comparison with hyaluronic acid and control group. Besides, histological finding of our material revealed that in general terms had all the hallmarks of complete healing two weeks post operatively. Conclusion: Our novel material appeared to have outstanding effect on periodontal wound healing which can improve the periodontal healing consequences and provide better strength of periodontal wound flap. From a clinical standpoint, it could play an important role for better repair in diabetic patients who frequently present difficulties in mucosal and cutanous wound healing.

Characteristic of hyaluronic acid derivative films cross-linked by polyethylene glycol of low water content

Objective:To test the characteristics of hyaluronic acid(HA)derivative cross-linked by polyethylene glycol films of low water content.Methods:The cross-linked HA film with 200μm thickness was got at atmospheric pressure at 25℃for 5 d.After dried,cross-linked films of 10 mm×10 mm were weighed and immersed in phosphate buffered saline (PBS pH 7.45)at 37℃for 24 h.Then the solution fraction and water content were estimated.Meanwhile,cross-linked HA derivative films were immersed in phosphate buffered saline(PBS:pH 7.45)at 37℃for determined time and then implanted subcutaneously in the back of white rats to test in vitro or in vivo degradation characteristic.Results and Conclusion:HA hydrogel cross-linked by polyethylene glycol with water content is as low as 60% and this kind of HA derivative has a slow degradation rate.

Preparation and Characterization of AlginateHyaluronic Acid-chitosan based Composite Gel Beads

The aim of this study was to fabricate composite gel beads based on natural polysaccharides. Hyaluronic acid（HA） and Chitosan（CS） were successfully admixed with Ca^2＋/alginate（SA） gel system to produce SA/HA/CS gel beads by dual crosslinking： the ionic gelation and the polyelectrolyte complexation. The preparation procedure was that the weight ratio of SA（2%, m/v） to HA（2%, m/v） was kept at 2：1, then the mixture was dripped into the Ca^2＋ solution for ion-crosslinking, and finally polyelectrolyte crosslinked with 2% low molecular weight CS（LMW-CS） for 1.5 hours. The optimal formulation was achieved by adjusting the concentration and the weight ratio of SA, HA and LMW-CS. Due to the incorporation of HA and LMWCS, the swelling ratio of the beads at pH 7.4 was increased up to 120, and the time for the maximum swelling degree was prolonged to 7.5 h. The swelling behavior was obviously improved compared to the pure SA/Ca^2＋ system. The preliminary results clearly suggest that the SA/HA/CS gel beads may be a potential candidate for biomedical delivery vehicles.

CHAP-Hyaluronic Acid (CHAP-HA) Filler as an Optimal Candidate for Forehead Filler Augmentation Using a 3-Point Injection Technique

Minimally invasive forehead augmentation is becoming increasingly popular in Asia. However, treatment of the glabella is associated with injection-related complications. The safety of injections can be increased through a thorough understanding of the anatomy and precise injection planes. The authors propose a 3-point injection technique for forehead augmentation in Asian patients that uses CHAP-hyaluronic acid (CHAP-HA) filler. The longevity of the filler was assessed using high-resolution ultrasound (HRU) imaging. Fifteen patients were examined using HRU before and immediately after treatment and at 1 month, 3 months, 6 months, and 12 months. As evident in HRU imaging, CHAP-HA remained visible within surrounding tissue for 6.4 ± 3.7 months. The mean Global Aesthetic Improvement Scale rating was 2.4 ± 0.5 immediately after treatment, 2.8 ± 0.3 at 1 month, 2.7 ± 0.5 at 3 months, 2.1 ± 0.6 at 6 months, and 1.5 ± 0.6 at 12 months. Minimal side effects were reported. The authors demonstrated that CHAP-HA filler may be an optimal candidate for forehead filler augmentation using a 3-point injection technique.

An Association of Vitamins A and E with Hyaluronic and Lactobionic Acids may Prevent Molecular Changes Associated with Keratocyte to Myofibroblast Transition

Inflammatory events in the corneal stroma may activate keratocytes and trigger their transition towards myofibroblasts,which now produce different extracellular matrix(ECM)proteins thus causing corneal opacification.Corneal haze is a frequent side effect after photorefractive keratectomy(PRK)to correct high myopia.Currently,a preventive treatment with mitomycin-c can be used to limit the occurrence of this phenomenon.However,mitomycin-c is a toxic drug,not devoid of side effects,which may occasionally involve the corneal endothelium.Therefore,we have searched for a less risky,natural way,to prevent keratocytes transition.To this purpose,we have used as markers of the phenotype switch the proteins lumican(highly expressed by keratocytes and much less by myofibroblasts)and smooth muscle actin(αSMA)(highly expressed by myofibroblasts and poorly found in keratocytes),beside Fibronectin(Fn),the expression of which is also increased by transforming growth factor-beta(TGFβ)treatment.Treatment of human keratocytes with TGFβwas used to induce the protein shift.Among different possible candidates,we have found that vitamins A and E,hyaluronic and lactobionic acids may prevent,either alone,or much better in association,the shift in the ratio between lumican andαSMA and the increased Fn expression.In conclusion,it could be speculated that topic treatment of the ocular surface with an association of these four compounds could be able to prevent or at least limit the occurrence of post-PRK corneal haze,with the additional advantage of lubrication,hydration and antioxidant defense exerted by these molecules.

Clinical Study on Facial Rejuvenation of Non-crosslinked Small Molecule Hyaluronic Acid Combined with Filorga NCTF®BOOST135 HA

Objective To observe the clinical application of non-crosslinked small molecule hyaluronic acid combined with Filorga NCTF®BOOST135HA in facial rejuvenation.Methods A total of 156 patients were selected from the outpatient department of our department from January 2017 to January 2018,including 36 males and 120 females.They were randomly divided into treatment group(82 cases)and control group(74 cases).The age of the treatment group was 25-50 years old,with an average age of 34 years old,while that of the control group was 26-48 years old,with an average age of 35 years old.group A was treated with non-crosslinked small molecule hyaluronic acid combined with Filorga NCTF®BOOST135 HA,while group B was treated with non-crosslinked small molecule hyaluronic acid alone.Through two methods,the facial skin state is analyzed and the therapeutic effect is evaluated.Results Follow-up for 3-6 months after treatment showed that 73 cases were satisfied and 9 cases were not satisfied in group A,with a satisfaction rate of 89.02%.In group B,52 cases were satisfied and 22 cases were dissatisfied,with a satisfaction rate of 70.27%.Conclusion Hyaluronic acid combined with Filorga NCTF®BOOST135 HA is better than hyaluronic acid alone in the treatment of facial rejuvenation,and patients obtain higher satisfaction.

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

入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与CHB肝纤维化严重程度的相关性及对疾病预后的预测价值

目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预后的预测价值。方法选取河南省中医院2021年3月至2022年3月收治的78例CHB肝纤维化患者作为研究组,选择同期78名健康体检者作为对照组。比较研究组和对照组及不同肝纤维化分期、不同炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平与肝纤维化分期、炎症活动分级的相关性。CHB肝纤维化患者治疗3个月后,根据患者预后分为预后良好和预后不良亚组,比较预后良好和预后不良患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平联合检测对CHB肝纤维化患者预后不良的预测价值。结果研究组入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ高于对照组(P<0.05);不同肝纤维化分期、炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ比较:S1<S2<S3<S4、G1<G2<G3<G4,差异有统计学意义(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与肝纤维化分期、炎症活动分级均呈正相关(P<0.05)。预后良好患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平均低于预后不良患者(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平联合预测肝纤维化患者预后不良的曲线下面积(AUC)优于各指标单一检测(P<0.05)。结论CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平均呈现高表达,且与肝纤维化分期、炎症活动分级密切相关,其联合检测对CHB肝纤维化患者预后有较高的预测价值,可用于评估CHB肝纤维化患者病情严重程度和预后,为制定针对性治疗措施提供参考。