BACKGROUND:Crosslinked sodium hyaluronate gel has good mechanical property,biocompatibility,and biodegradability,and can be used as an isolated protective material in tumor radiation therapy to protect endangered organs from damage caused by excess radiation dose. OBJECTIVE:To investigate the safety and efficacy of crosslinked sodium hyaluronate gel in reducing the dose of radiation to dangerous organs during brachytherapy. METHODS:A total of 16 specific pathogen-free Kunming mice of the same age and similar body weight were selected as experimental subjects and divided into experimental group and control group by the random number table method,with 8 mice in each group.125I seeds were implanted subcutaneously in the back of mice in the experimental group,and then crosslinked sodium hyaluronate gel was injected around the radioactive particles.Only 125I seeds were implanted subcutaneously in the back of mice in the control group.After injection,the distance between the radioactive particles and the epidermis was measured by spiral CT scan,and the surface radiation dose was measured by radiation dosimeter.Within 10 weeks after injection,the growth state,survival rate,skin radiation damage,and gel retention of mice were observed. RESULTS AND CONCLUSION:(1)Spiral CT scan showed that the implanted gel was relatively concentrated and created an effective distance between the radioactive seeds and the epidermis.The body surface radiation dose of the experimental group was significantly lower than that of the control group(P<0.01).(2)During the experimental observation period,mice in both groups survived;mice in the control group showed obvious irritability and other unstable behavior in the late experimental period,and some mice in the experimental group showed similar behavior.The daily food intake of mice in the two groups had no significant change,and the body mass showed the same increasing trend.After implantation of radioactive seeds,the two groups of mice showed different degrees of radioactive skin injury.From day 23 after injection to the end of the experiment,the skin radiation injury score of the experimental group was lower than that of the control group(P<0.01).At week 10 after implantation,6 mice in the experimental group had no obvious gel residue under their skin,and 2 mice had a very small amount of scattered gel-like samples under their skin.(3)Therefore,the crosslinked sodium hyaluronate injection technique can increase the space between the radioactive target area of 125I seeds and the organ at risk outside the target through physical space occupying,which can effectively reduce the dose of the organ at risk,and play a role in the isolation and protection of the organ at risk.

Objective: To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation (FMT) in patients with type 2 diabetes mellitus (T2DM), and to preliminarily identify the traditional Chinese medicine (TCM) syndrome element characteristics of FMT in the treatment of T2DM. Methods: Between March 25, 2023 and September 30, 2024, T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. Participants received oral microbiota capsules as an adjunct to metformin therapy. Information obtained by four diagnostic methods of TCM, along with clinical and laboratory parameters, was collected before and after the intervention. Metagenomic sequencing was employed to analyze the gut microbiota, and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera. According to the post-treatment reduction in glycosylated hemoglobin (HbA1c), patients were categorized into a response (R) group and a non-response (NR) group. Treatment outcomes, safety indicators, gut microbiota changes, and TCM syndrome element features were compared between the two groups. Results: A total of 53 T2DM patients were included in the final analysis, and 30 patients were assigned to R group and 23 to NR group. After treatment, the R group exhibited significant reductions in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (2hPG) (P < 0.05 or P < 0.01). The NR group also showed significant decreases in HbA1c and FPG levels P < 0.01 or P < 0.05. Compared with the NR group, after treatment, FPG level in the R group demonstrated significant reductions (P < 0.01). As compared with before treatment, pancreatic islet function demonstrated enhancement in the R group, a significant increase in the 2-hour pastprandial C-peptide (2hC-P) levels in R group (P < 0.05), whereas no marked change was observed in the NR group. Regarding body composition indicators, the R group showed significantly lower waist-hip ratio (WHR), visceral fat (VF), and subcutaneous fat (SF) levels compared with the NR group (P < 0.01). After treatment, the NR group exhibited a significant elevation in aspartate aminotransferase (AST) levels (P < 0.05). Other safety-related indicators fluctuated within normal reference ranges, and no other adverse events, such as diarrhea, fever, or nausea, were reported. Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota, remodeling its overall structure. At the phylum level, the abundance of p_Firmicutes decreased significantly (P < 0.01), while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly (P < 0.01). At the family level, among the 125 identified taxa, the abundances of f_Bacteroidaceae, f_Lactobacillaceae, and f_Sutterellaceae were significantly elevated, whereas six families, including f_Lachnospiraceae, f_Ruminococcaceae, and f_Coriobacteriaceae, were significantly decreased (all P < 0.05). Among the 367 taxa at the genus level, the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella, and significantly decreased abundances in eight genera, including g_Faecalibacterium, g_Ruminococcus, g_Blautia, and g_Collinsella (all P < 0.05). Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters, g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide (FC-P) and 2hC-P (P < 0.05). HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger (P < 0.05) and a significantly negative correlation with g_Bacteroides and g_Collinsella (P > 0.05). Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness, phlegm, and Yang deficiency. Before treatment, statistically significant reductions in syndrome element scores were observed for dampness, Yang deficiency, spleen, phlegm, Qi deficiency, Qi stagnation, and Yin deficiency (P < 0.01), as well as for heat and liver (P < 0.05). The NR group was mainly featured with Qi deficiency and Yin deficiency. Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency (P < 0.01), and for spleen, Qi stagnation, liver, and blood deficiency (P < 0.05). In this group, the score changes for Yang deficiency, Yin deficiency, heat, and dampness were not statistically significant (P > 0.05). Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM. Patients with T2DM presented with specific TCM syndrome element characteristics, notably dampness, phlegm, and Yang deficiency, represent a highly responsive population to FMT therapy.

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC₅₀） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （K_off） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC₅₀ values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller K_off values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Objective To analyze the effect and molecular mechanism of phellodendron amurense in the treatment of liver injury based on network pharmacology,and to verify the relevant prediction targets and the protective effect of phellodendron amurense extract-Phellodendron amurense polysaccharide on immune liver injury through mice.Methods TCMSP and Swiss target prediction databases were used to retrieve and screen phellodendron amurenses active components and action targets,and then obtain disease-related targets on GeneCards and OMIM websites,and take compounds and disease intersection targets for protein interaction.Analysis,GO biological function and KEGG signaling pathway enrichment analysis,followed by molecular docking of compounds and key target proteins,and finally established a mouse liver injury model induced by Daodou protein A(Con A)to explore the mechanism of phellodendron amurense extract in the treatment of liver injury.Results 37 active ingredients were screened.The key targets for their treatment were tumor necrosis factor α(TNF-α),serine/threonine protein kinase 1(AKT1),signal transduction and transcription activation factor 3(STAT3),epidermal growth factor receptor(EGFR)anditin.Enzyme 3(CASP3)and other enrichment analysis showed that phellodendron amurense might play a protective role in protecting the liver through molecular mechanisms such as positive regulation of MAPK cas-cade reaction,oxidative stress response and regulatory PI3K-Akt signaling pathway,lipid and atherosclerosis.Ani-mal experiments had found that the gastric treatment of phellodendron amurense polysaccharide could improve the activity of superoxide dismutase(SOD)and catalase(CAT)in liver tissue,reduce the levels of serum alkaline phosphatase(ALP),aspartate aminotransferase(AST)and malonaldehyde(MDA)in liver tissue,and regulate serum inflammatory factor while the expression of intercitin(IL)-6,IL-1 β,tumor necrosis factor α(TNF-α),ac-tivated the expression of transforming growth factor β1(TGF-β1),and reduced TNF-α mRNA expression in liver tissue.Conclusion Phellodendron amurense can intervene in lipid and atherosclerosis pathways by acting on tar-gets such as TNF-α,AKT1,STAT3,EGFR and CASP3 to reduce oxidative stress and inflammatory reactions and achieve liver protection.

Objective:To evaluate the effect of nursing specialist nurses′ assistance on the ability of nursing home nurses to maintain venous catheter under the vision of combination of medical care and nursing care, providing reference for carrying out specialized nursing assistance work in grassroots hospitals.Methods:This study was an experimental study. According to Miller′s pyramid theory, a model of specialist nurse assistance was established with specialized technology as the core. From January to December 2021, three nursing hospitals in Suzhou were assisted. Convenience sampling method was used to investigate the ability of intravenous catheter maintenance, the incidence of central venous catheter maintenance defects, the incidence of central venous catheter complications and unplanned extubation, and the satisfaction of doctors and patients before and after help.Results:Totally 86 nurses were included, aged (33.17 ± 2.31) years old. After the help, the theoretical and operational skill scores of nurses in the nursing home were (89.77 ± 2.11) and (92.75 ± 1.62) points, respectively, which were significantly higher than those before the help (60.84 ± 2.71) and (79.81 ± 1.68) points, and the differences were statistically significant ( t=-84.96, -52.12, both P<0.05). Among the maintenance defects of central venous catheter in nursing homes, incomplete labeling, film wrapping, blood seepage, catheter discounting, non-standard film fixing, and incomplete information of extended care were 9.95% (21/211), 8.53% (18/211), 2.84% (6/211), 6.16% (13/211), 4.74% (10/211), 2.37% (5/211) after help, all lower than 50.57% (89/176), 43.18% (76/176), 14.20% (25/176), 25.57% (45/176), 18.18% (32/176), 11.93% (21/176) before help. The differences were statistically significant ( χ2 values were 14.00 to 77.81, all P<0.05). The incidence of medical adhesive related skin injury, catheter obstruction complications and unplanned extubation were 4.44% (4/90), 3.33% (3/90) and 2.22% (2/90), respectively, which were lower than 20.51% (16/78), 15.38% (12/78) and 11.54% (9/78) before help. The differences were statistically significant ( χ2=8.81, 6.06, 4.50, all P<0.05). Doctors′ satisfaction with nurses and patients′ satisfaction with nursing work were 96.43%(27/28) and 93.75%(45/48), respectively, both higher than 71.43%(20/28) and 72.73%(32/44) before help, and the differences were statistically significant respectively ( χ2=4.77, 5.97, both P<0.05). Conclusions:From the perspective of combination of medical care and nursing care, the maintenance and assistance of intravenous catheters by the team of intravenous therapy nurses in nursing hospitals can effectively reduce the incidence of central venous catheter complications and unplanned extubation, improve the maintenance ability of intravenous catheters of nurses in nursing hospitals, and help to improve the quality of nursing care in nursing hospitals.

BACKGROUND:The specific mechanism of Gushukang,as a Chinese traditional patent medicine for the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis,needs further studies. OBJECTIVE:To investigate the effect of Gushukang on serum sex hormones,bone microstructure and estrogen receptor in postmenopausal osteoporosis. METHODS:Firstly,network pharmacological analysis was performed.The active ingredients and action targets of Gushukang and the targets of postmenopausal osteoporosis were obtained respectively.Cytoscape was used to construct the active ingredient-target network.STRING database and Cytoscape were used for protein-protein interaction analysis and screening of core targets.DAVID database was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersection targets.Then the ovariectomized Sprague-Dawley rats were used in the animal experiment.Gushukang was administered by gavage for 3 months.The serum estrogen level was detected by ELISA,the bone microstructure was detected by microCT,and the protein expression of estrogen receptor α and estrogen receptor β in bone tiusse was detected by western blot. RESULTS AND CONCLUSION:The network pharmacological research results identified 132 active ingredients and 150 targets of Gushukang and 1155 targets of postmenopausal osteoporosis.After intersections with 1155 postmenopausal osteoporosis targets,87 targets of active ingredients of Gushukang against postmenopausal osteoporosis were obtained.By constructing the active ingredient-target network,it was found that the active ingredients at the core were quercetin,kaempferol,luteolin,naringin and isorhamnetin,and the targets at the core were NCOA2,ESR2,AR,F2,ESR1 and PTGS1.The final targets obtained after the protein-protein interaction analysis and screening included MAPK8,ESR1,JUN,R3C1,RELA and FOS,of which ESR1 was the common core target obtained from the two analyses.KEGG enrichment analysis showed estrogen,tumor necrosis factor,apoptosis and other signaling pathways.Therefore,animal experiments focused on the effect of Gushukang on different subtypes of estrogen receptors in the estrogen signaling pathway.The results showed that in the Gushukang group,bone microstructure was significantly improved,serum estrogen level had no significant change,but the protein expression of estrogen receptor α and β in bone tissue was significantly increased.All the findings indicate that the mechanism of Gushukang in the treatment of postmenopausal osteoporosis may be related to its hormone-like effect and the enhancement of estrogen receptor expression.