BACKGROUND:The structure,physical and chemical properties(such as rheological properties)and biological activity of hyaluronic acid with different molecular weights are quite different.When the degradation degree of non-cross-linked hyaluronic acid is too large and the high-molecular-weight hyaluronic acid is degraded to low-molecular-weight hyaluronic acid,the properties and biological functions of the product will also change,which will affect the use of the product. OBJECTIVE:To review the mechanism of molecular weight degradation of non-cross-linked hyaluronic acid and the impacts of molecular weight degradation on the structure,rheological properties,biological activity and applications of non-cross-linked hyaluronic acid. METHODS:The first author searched the articles related to the molecular weight of hyaluronic acid collected in PubMed,CNKI database and other databases.The high-quality articles with high correlation were screened according to the inclusion and exclusion criteria.The search time was from January 2017 to December 2022.The Chinese and English search terms were"hyaluronic acid,non-cross-linked hyaluronic acid,molecular weight,degradation,structure,rheological properties,biologic activity".Finally,47 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The molecular weight of non-cross-linked hyaluronic acid is mainly degraded by specific enzymatic hydrolysis and non-specific free radical degradation.(2)The molecular weight degradation of non-cross-linked hyaluronic acid will change its structure and rheological properties,resulting in the untie of polymer network structure,the decrease of rheological properties such as viscosity and viscoelasticity,and the decrease of mechanical properties,which will eventually affect the practical application effect of the product.(3)The biological activity of non-cross-linked hyaluronic acid is molecular weight dependent,and the biological activity of different molecular weight hyaluronic acid is different.Even the same receptor combined with high-molecular-weight hyaluronic acid and low-molecular-weight hyaluronic acid will express completely opposite biological effects.(4)The degradation of molecular weights of non-cross-linked hyaluronic acid will reduce the safety and efficacy of the products,affect their service life and application performance,and ultimately influence the clinical application results.(5)Non-cross-linked hyaluronic acid has great potential as a biodegradable biomaterial in wound healing,tissue engineering,aesthetic medicine and other fields,and further research and understanding of the correlation between molecular weight degradation of non-cross-linked hyaluronic acid and bioactivity is a prerequisite for better development of wound dressings,drug delivery systems and tissue-engineered scaffolds.(6)However,there are currently few studies on the molecular weight degradation of non-cross-linked hyaluronic acid,and it is unclear how to effectively avoid the potential risks associated with the molecular weight degradation of non-cross-linked hyaluronic acid in clinical applications.(7)Therefore,a series of potential risks associated with the molecular weight degradation of non-cross-linked hyaluronic acid during its application,including the effects on its structure,properties and biological activity,and the resulting changes on the body,is one of the future directions that need to be closely investigated.

Objective:Assisted traction technology is effective in increasing the rate of super minimally invasive surgery (SMIS) in patients with early gastric cancer (EGC), and shortening the operator′s learning curve. We adopt the variable angle traction technique of tissue clamp dental floss as a traction technique in this research.Methods:Patients with early gastric cancer who were treated with SMIS - non full layer resection of EGC were enrolled in the First Medical Center of Chinese PLA General Hospital from January 2022 to June 2023. This research was carried out by experts at the same level. It was divided into two groups: traction and non-traction. Submucosal detachment time (SDT), submucosal detachment rate (SDS), lamina propria exposure, muscularis propria defect (MPD), bleeding during operation, block resection, surgical resection, hand operation expenses, and surgical instruments were recorded.Results:Nine patients adopted variable angle traction, and 9 patients did not. The overall resection rate and curative resection rate of both groups were 100%. The mean SDT time was 28.00 (21.00, 34.00) min in traction group and 56.00 (40.00, 85.00) min in non traction group. And it had statistical significance ( P = 0.005). The SDS was (0.58 ± 0.21) cm 2/min in traction group and (0.23 ± 0.10) cm 2/min in non-traction group. And it had statistical significance ( P<0.05). Exposure of intrinsic muscle layer (IML): 8 cases in the traction group and 6 cases in the non-traction group. Intraoperative IML injury: in the traction group, 8 cases were MPD-0 and 1 case was MPD-Ft; in the non-traction group, 4 cases were MPD-0, 1 case was MPD-Pt, and 4 cases were MPD-Ft. There was no statistical difference between the two groups in terms of intraoperative bleeding, hospitalization expenses, surgical expenses, and the total hospitalization time. There were no serious adverse reactions or outcomes. Conclusions:The variable angle traction method accelerates SDT and SDS for SMIS-non full layer resection of EGC. It has the advantages of the sufficient separation of IML and mucosal layer, the deeper dissection depth, the low injury of IML, low intraoperative bleeding, and no additional medical costs. Therefore, this method can become an auxiliary treatment technology for SMIS.

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

Objective:To investigate the clinical characteristics and voice outcomes after laryngeal microsurgery for vocal fold epidermoid cysts coexisting with sulcus vocalis.Methods:The clinical data of 115 vocal fold epidermoid cysts coexisting with sulcus vocalis patients in Shandong provincial ENT hospital, were retrospectively analyzed, including 49 males and 66 females, aged 17-70 years old, and the duration of hoarseness ranged from 6 months to 30 years. All patients underwent surgery through suspension laryngoscope and microscope under general anestgesia. Ninety-four patients were treated with microflap excision of sulcus vocalis, cyst wall, and contents.And 21 patients that occulted with mucosal bridges were applied mucosal bridges resection (2 cases) and mucosal bridges reconstruction (19 cases) respectively. Videolaryngoscopy, subjective voice evaluation (GRBAS), objective voice evaluation, and Voice Handicap Index(VHI) were performed before and after surgery. All patients underwent histopathologic examination and follow-up after the procedure. The preoperative acoustic parameters of patients with vocal fold epidermoid cysts coexisting with sulcus vocalis were compared with those of vocal fold mucus retention cysts and simple vocal fold epidermoid cysts by independent samples t-test. The patients were compared by paired t-test for preoperative and postoperative parameters. Results:Significant reduction or lack of mucosal waves were shown via videolaryngostroboscopy in all 115 cases.In addition, vascular changes including dilation, tortuousness, increased branches, and abrupt direction change were shown on the cystic area. Eighty-one patients were detected cysts and/or sulcus vocalis by preoperative laryngoscopy, and intraoperative microscopic findings in the remaining 34 patients. The intraoperative microscopic examination revealed a focal pouch-like deficit plunging into the vocal ligament or muscle. The deep surface of the mucosal bridges was sulcus vocalis, and that in 89 cysts was lined with caseous content. Histopathology demonstrated a cystic cavity structure lined with squamous epithelium and caseous keratin desquamation inside the cystic cavity. Four of 115 patients were lost at follow-up and excluded from the analysis of voice outcomes after surgery. There was no significant mucosal wave and the voice quality in all but 14 patients 1month after surgery. Except for the fundamental frequency and noise harmonic ratio, all other voice parameters[ G, R, B, A, VHI-10, jitter, shimmer, maximum phonatory time (MPT) ]showed a significant improvement 3 months after surgery( t=15.82, 20.82, 17.61, 7.30, 38.88, 7.84, 5.88, -6.26, respectively, P<0.05). Then mucosal waves and the voice quality were gradually improved and became steady in 6 months after surgery. The subjective and objective voice parameters[G, R, B, A, VHI-10, jitter, shimmer, noise to harmonic ratio(NHR), MPT], except for the fundamental frequency, were all significantly improved( t=23.47, 25.79, 18.37, 9.84, 54.45, 10.68, 8.07, 3.24, -9.08, respectively, P<0.05). In addition, there were 2 patients with no significant improvement after the operation. Steady function with no complications was observed during the 12 months (up to 3 years in 34 patients) follow-up period in 111 patients. Conclusion:Ruptured vocal fold epidermoid cysts can result in sulcus vocalis and mucosal bridges. Characteristics changes in preoperative videolaryngoscopy are effective diagnostic tools. The complete excision of the cyst wall and repair of the lamina propria can lead to satisfactory long-term effects.

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.

Objective:To preliminarily predict the potential pathways and targets of Xiaoban Tongmai Formula in anti-atherosclerosis(AS)by network pharmacology analysis,and to verify its possible mechanism combined with in vitro cell experiment.Method:The databases including Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GeneCards,Swiss Target Prediction,and Uniprot were used to collect the information on active compounds and corresponding targets of Xiaoban Tongmai Formula to construct the"compound-target-disease"network.The potential targets and pathways were predicted by protein-protein interaction(PPI)network,and the intersection targets were subjected to Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The human aortic vascular smooth muscle cells(HA-VSMCs)were cultured and identified in vitro,and the abnormal proliferation of HA-VSMCs were induced by oxidized low-density lipoprotein(ox-LDL)and identified;MTT method was used to detect the proliferation activities of the HA-VSMCs in various groups after treated with different concentrations of Xiaoban Tongmai Formula;the safety of Xiaoban Tongmai Fang was confirmed.The HA-VSMCs were divided into blank group,model group(the abnormal proliferation of HA-VSMCs was induced),rosuvastatin group(treated with 4 μmol·L-1 rosuvastatin after inducing the abnormal proliferation of HA-VSMCs),and low,medium,and high doses of Xiaoban Tongmai Formula groups(treated with 0.025,0.050,and 0.100 mng·L-1 Xiaoban Tongmai Formula after inducing the abnormal proliferation of HA-VSMCs);enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-6(IL-6),and interleukin-8(IL-8)in supernatant of the HA-VSMCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of nuclear factor kappa-B(NF-κB)p65 mRNA and fibroblast growth factors 2(FGF2)mRNA in the HA-VSMCs in various groups;Western blotting method was used to detect the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in various groups.Results:Xiaoban Tongmai Formula contained 103 active ingredients that exert anti-AS effect by acting on 189 target genes.The potential targets included IL-6,IL-8,vascular endothelial growth factor A(VEGFA),nuclear factor kappa B1(NF-κB1),and RELA(NF-κB p65).The GO functional analysis and KEGG pathway enrichment analysis results showed that Xiaoban Tongmai Formula exerted anti-AS effects by regulating lipid metabolism,hypoxia-inducible factor-1(HIF-1),epidermal growth factor(EGF),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),and NF-κB signaling pathways.The cell morphology and immunofluorescence staining results confirmed that the cells were HA-VSMCs.The oil red O staining results showed numerous red lipid droplets,indicating successful modeling.The MTT assay results showed that Xiaoban Tongmai Formula had no significant effect on the proliferation rate of HA-VSMCs within a certain dose range,indicating good safety.The ELISA results showed that compared with model group,the levels of MCP-1 and IL-6 in supernatant of the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the levels of MCP-1 in supernatant of the HA-VSMCs in different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01).Compared with model group,the expression levels of NF-κB p65 mRNA in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression levels of FGF2 mRNA in the HA-VSMCs in rosuvastatin group and 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 and FGF2 mRNA in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01).Compared with model group,the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 protein in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression level of FGF2 protein in the HA-VSMCs in 0.100 mg·L-1 Xiaoban Tongmai Formula group was decreased(P＜0.01).Conclusion:Xiaoban Tongmai Formula has anti-inflammatory effect,inhibitory effect on the proliferation of HA-VSMCs,and anti-AS effect,and its mechanism may be related to the inactivation of NF-κB/FGF2 pathway.

Adhesives have emerged as an effective method for wound closure,hemostasis and tissue engineering in recent years,which not only are suitable for the adhesion of wet tissues,but also can adapt to the peristalsis and mechanical stretching of tissues and organs,especially for arteries and organize bleeding.With the further development of technology,existing adhesives can be modified through different strategies,and new materials are explored,giving new properties and uses to adhesives,such as drug delivery,temperature sensitivity,light sensitivity and so on.Nevertheless,there are many questions about the design and practical clinical application of adhesives in the future.The recent research progress of traditional adhesives and their application in hemostasis is reviewed,and the design and development ideas of future adhesives are discussed in the study.

Objective:To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses.Methods:A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP.Results:Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed.Conclusions:When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.

Colon cancer is one of the most common malignant tumors worldwide.When the conventional treatment methods provide survival benefits for patients,their side effects and limitations cannot be ignored.Many traditional Chinese medicines has attracted much attention from scholars at home and abroad because of its anti-tumor advantages of multi-target,multi-pathway and less toxic side effects.Many Chinese medicines and the active components extracted from them,represented by flavonoids,phenols and alkaloids,have played an effective role in anti-tumor.There mechanism is related to inhibiting tumor cell proliferation,inducing apoptosis,regulate autophagy,inhibiting tumor cell invasion and metastasis,inhibiting tumor angiogenesis.In this paper,the mechanism of inhibiting colon cancer by effective components of traditional Chinese medicine in recent years was reviewed in order to provide reference for the clinical treatment of colon cancer.

Objective:To understand the dilemma of active management in young and middle-aged postoperative patients with lumbar disc herniation, in order to provide reference for the formulation of active intervention program of self-health management meeting the needs of patients.Methods:Using the phenomenological research method, a total of 16 middle-aged and young patients with lumbar disc herniation were selected for semi-structured in-depth interviews, and the themes were analyzed and extracted by Colaizzi 7-step analysis method.Results:Three themes and nine sub-themes were extracted namely, inadequate disease response capacity and response resources (lack of disease symptom management capacity, limited access to disease management information, difficult use of disease management information, difficulty in maintaining positive self-management for a long time (forced to stop behavior change due to stress, lack of motivation to achieve good behavior change, doubts about the effectiveness of self-management) and multi-dimensional negative emotions (contrast between maintaining independence and dependence on others, fear of being misunderstood, fear of relapse) .Conclusions:Medical staff should provide comprehensive health information services for young and middle-aged postoperative patients with lumbar disc herniation, improve the out-of-hospital follow-up mechanism with the help of information technology, further improve family and social support strategies, reduce the difficulties faced in the process of active management and achieve long-term active disease management.