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.

BACKGROUND:With the development of biomechanics,its research into cardiovascular diseases has become more and more extensive.By studying the mechanical properties of blood vessels,the pathogenesis of cardiovascular diseases such as atherosclerosis and restenosis can be effectively revealed and new ideas and methods can be developed for the treatment of cardiovascular diseases. OBJECTIVE:To review the research status of apoptosis of vascular smooth muscle cells induced by mechanical stress and search for potential target molecules and signaling pathways for clinical treatment,thereby improving the clinical treatment effect on cardiovascular diseases such as atherosclerosis and restenosis. METHODS:We searched the literature in CNKI,PubMed and ScienceDirect databases from January 1992 to May 2023.The search terms were"vascular smooth muscle cell,mechanical stress,shear stress,stretch stress,apoptosis"in Chinese and English.Finally,63 articles were included for review and analysis. RESULTS AND CONCLUSION:Physiological and pathological apoptosis of vascular smooth muscle cells is an adaptive remodeling in response to the changes in vascular mechanics.Vascular smooth muscle cells in different parts have different mechanical stimuli and their pathogenesis is also different.Low shear stress,physiological shear stress and high shear stress directly interact with surface molecules,receptors and proteins of vascular smooth muscle cells to regulate apoptosis-related signaling molecules and inhibit cell proliferation,thus regulating the apoptosis of vascular smooth muscle cells.In this part,the research on promoting proliferation is not summarized.Low stretch stress,physiological stretch stress and high stretch stress can all cause apoptosis of vascular smooth muscle cells,but it is still controversial.There are many mechanoreceptors(such as integrins and receptor tyrosine kinases)on the surface of vascular smooth muscle cells,which can transform mechanical signals into intracellular chemical signals(such as the Hippo pathway),activate the apoptosis signals of vascular smooth muscle cells and regulate the apoptosis of vascular smooth muscle cells.In short,different mechanical stimuli start a variety of signal pathways and regulate the apoptosis of vascular smooth muscle cells through various signal molecules.For example,shear stress affects Fas/FasL and Akt pathways mainly by stimulating prostaglandin secretion and transforming growth factors.Strech stress mainly regulates the YAP pathway and Notch pathway through Yes-related proteins.At different times or intensities,these molecules may play opposite two-way roles.For example,when mouse vascular smooth muscle cells are stretched at 10%physiological tension for 1 hour,cell proliferation increases.However,the proliferation of human vascular smooth muscle cells can decrease after 12 hours of stretching.Clinically,the key molecules of mechanical transduction can be disturbed by searching for key molecules that interfere with mechanical transduction at their critical time points of action.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To investigate the influencing factors of urinary system symptoms in urban and rural residents aged 35 years old and above in Anhui province.Methods:A total of 19 339 residents aged 35 years old and above were selected from 19 counties(districts)of 9 cities in Anhui Province by multi-stage stratified cluster random sampling method.Binary logistic regression was used to analyze the influencing factors of urinary system symptoms.Results:There were statistically significant differences among different gender,age,long-term residence,body mass index and education level in the other 3 symptoms except urinary secretions(P＜0.05).Binary logistic regression analysis model showed that with the increase of age,the risk of frequent urination/urgent urination/painful urination,eyelid or lower limb edema increased,OR values were all＞1.Body mass index≥24 kg/m2 was the risk factor of frequent urination/urgent urination/painful urination,eyelid or lower limb edema(P＜0.05).People who lived in rural areas for a long time had a lower risk of blood urination(OR=0.79,P＜0.05).The risk of urinary secretions decreased with the improvement of education level(P＜0.05).Diagnosed diabetes,use of analgesics(ibuprofen/butazon/indola,etc.),heavy dietary taste was(like to eat pickled/smoked/fried/spicy food),long-term heavy physical work(carrying heavy objects/digging/clearing snow/chopping wood,etc.),and sleep time＜8 h were the risk factors of these four urinary symptoms(P＜0.05).Long-term drinking was a risk factor for frequent urination/urgent urination/painful urination symptoms(OR=1.02,P＜0.05).Conclusion:Personal characteristics,diabetes mellitus,dietary habits,medication history and physical activity have a certain influence on the occurrence of urinary system symptoms.

The widespread application of implantable materials has brought about a corresponding increase in implant-related complications, with implant-associated infections being the most critical. Biofilms, which often form on these implants, can significantly impede the effectiveness of traditional antibiotic therapies. Therefore, strategies such as surgical removal of infected implants and prolonged antibiotic treatment have been acknowledged as effective measures to eradicate these infections. However,the challenges of antibiotic resistance and biofilm persistence often result in recurrent or hard-to-control infections, posing severe health threats to patients. Recent studies suggest that phages, a type of virus, can directly eliminate pathogenic bacteria and degrade biofilms. Furthermore, clinical trials have demonstrated promising therapeutic results with the combined use of phages and antibiotics. Consequently, this innovative therapy holds significant potential as an effective solution for managing implant-associated infections. This paper rigorously investigates and evaluates the potential value of phage therapy in addressing orthopedic implant-associated infections, based on a comprehensive review of relevant scientific literature.

Objective To investigate the efficacy and safety of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods A total of 84 patients with advanced HCC admitted to our hospital from January to December 2020 were selected as the study objects,and were randomly divided into the observation group and the control group,with 42 cases in each group.Patients in the observation group received intensity-modulated radiation therapy combined with carrelli-zumab,and patients in the control group received intensity-modulated radiation therapy.The short-term efficacy,immune function and long-term survival rate of patietns in the two groups were compared,and the incidence of adverse reactions was recorded.Results The total effec-tive rates of the observation group 1 month and 3 months after treatment were significantly higher than those of the control group(P<0.05).The levels of CD3+,CD4+ and CD4+/CD8+ 1 month and 3 months after treatment were all increased in the two groups,while the levels of CD8+ in both two groups were decreased(P<0.05),and the levels of CD3+,CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group(P<0.05),and the levels of CD8+ in the observation group were lower than those in the control group(P<0.05).The median survival time of patients in the observation group was significantly longer than that of patients in the control group(P<0.05).The incidence of cutaneous capillary hyperplasia in the observation group was higher than that in the control group(P<0.001),and there was no significant difference in the incidence of other adverse reactions between the two groups(P>0.05),and all of adverse reactions were grades 1 to 2.Conclusion Intensity-modulated radiation therapy combined with camrelizumab has a good effect on HCC,it can improve the immune function of the body,and control the development of the disease,with good safety.

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.