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.

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

Objective To explore the differences of regional homogeneity(ReHo)between overweight and normal weight male patients with type 2 diabetes mellitus(T2DM)during rest and their correlations with clinical features.Methods Twenty-five untreated male overweight T2DM(OW-T2DM)patients,25 untreated male normal weight T2DM(NW-T2DM)patients and 25 healthy controls(HC)were enrolled.The brain structure and resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from all subjects.The brain structure and rs-fMRI data were preprocessed,and ReHo values of all brain regions were calculated for all subjects.ReHo values were compared among three groups and between groups respectively via the methods of one-way analysis of variance and two-sample t-test.To address the problem of multiple comparisons,the method of AlphaSim was performed(the threshold was set at P<0.005,the number of voxel clusters was>12).In addition,Pearson correlation analysis was performed to explore the relationships between ReHo values of the abnormal brain regions and clinical features in patients.Results(1)The brain regions showed differences of ReHo values among three groups were mainly distributed in the right hemisphere,including the superior parietal gyrus,superior marginal gyrus and superior occipital gyrus;(2)Compared with HC,NW-T2DM patients showed significantly decreased ReHo values in the right medial superior frontal gyrus,right middle cingulate gyrus and left anterior cingulate gyrus;(3)Compared with HC,OW-T2DM patients showed significantly decreased ReHo values in the bilateral postcentral gyrus and bilateral middle cingulate gyrus;(4)Compared with NW-T2DM patients,OW-T2DM patients showed significantly decreased ReHo values in the right superior parietal gyrus,right superior occipital gyrus and left cuneus;(5)ReHo values of the right medial superior frontal gyrus and right superior parietal gyrus were negatively correlated with hemoglobinA1c(HbA1c)level and body mass index(BMI),respectively,in all patients.Conclusion The occurrence of T2DM in male patients may lead to the declined activity of brain regions located in the default mode network(DMN),while overweight may further lead to decreased brain activity within the attention and visual recognition network in male T2DM patients.

Objective To investigate the diagnostic value of the T2WI gray scale ratio for Hashimoto's thyroiditis(HT).Methods The T2WI-iterative decomposition of water and fat with echo asymmetry and least square estimation(IDEAL)quantitation sequence water images of 22 HT cases were analyzed retrospectively.The gray scale ratio of the thyroid,sternocleidomastoid muscle,trachea cavity,and subcutaneous fat at the same layer were measured on the picture archiving and communication systems(PACS).The gray scale ratios of thyroid/sternocleidomastoid muscle(T/M),thyroid/trachea cavity(T/Tr),and thyroid/lipid(T/L)were calculated.The intraclass correlation coefficient(ICC)was used to evaluate the consistency among the measurements,and the optimal threshold for distinguishing HT from non-HT was determined via the receiver operating characteristic(ROC)curve.The Spearman correlation analysis was used to analyze the correlation between T/M,T/Tr,T/L ratios,and titers of thyroid peroxidase antibody(TPO-Ab)and thyroglobulin antibody(Tg-Ab),respectively.Results On the T2WI-IDEAL quantitation sequence water images,the(x)±s of T/M,T/Tr,T/L ratios for HT and non-HT were 2.17±0.47 and 1.62±0.21(t=14.90,P<0.001),9.40±3.24 and 4.87±2.93(t=11.42,P<0.001),1.66±0.32 and 1.21±0.31(t=7.51,P<0.001),respectively.The area under the curve(AUC)of T/M,T/Tr,and T/L ratios for diagnosing HT were 0.89,0.86,and 0.85,respectively;the optimal thresholds were 1.90,3.50,and 1.36,and the sensitivity and specificity were 72.7%and 100%,100%and 40.5%,95.5%and 29.7%,respectively.The T/M ratio had a moderate correlation with TPO-Ab(r=0.513,P<0.05),and T/Tr,T/L ratios had a mild correlation with TPO-Ab,respectively.Conclusion The T/M ratio in the T2WI gray scale ratio can quantitatively and objectively distinguish HT from non-HT to some extent and is correlated with TPO-Ab.It has extremely high specificity and holds promise as a non-invasive imaging method for the diagnosis of incidental HT.

OBJECTIVE:At present,there are many reports on the related factors associated with the incidence of cervical spine instability in patients with rheumatoid arthritis,but there are problems such as small sample size and many confounding factors,and the research results of various studies on the same related factors are also different.This article analyzed the factors related to cervical spine instability in patients with rheumatoid arthritis by means of a systematic review. METHODS:Articles related to cervical spine instability in patients with rheumatoid arthritis were collected by searching both Chinese and English databases until March 2023.The outcome of cervical spine instability in patients with rheumatoid arthritis was used as the grouping criterion to abstract basic information,baseline patient characteristics,laboratory-related tests,medication use,and other relevant risk factors.Meta-analysis was done using Stata 14.0 software. RESULTS:(1)Sixteen relevant studies,all of moderate or above quality,were included,including seven studies with case-control studies and nine with cross-sectional studies.The overall incidence of cervical spine instability in patients with rheumatoid arthritis was 43.08%.(2)Meta-analysis showed:Related risk factors included female(OR=0.60,95%CI:0.44-0.82,P=0.002);age at disease onset(SMD=-0.52,95%CI:-0.86 to-0.18,P=0.003);duration of disease(SMD=0.58,95%CI:0.14-1.02,P=0.01);body mass index(OR=0.74,95%CI:0.63-0.88,P=0.001);rheumatoid factors positive univariate analysis subgroup(OR=1.33,95%CI:1.02 to 1.72,P=0.04),C-reactive protein(SMD=0.26,95%CI:0.16-0.35,P=0.00),erythrocyte sedimentation rate(SMD=0.15,95%CI:0.002-0.29,P=0.047),anti-cyclic-citrullinated peptide antibodies(OR=1.73,95%CI:1.19-2.51,P=0.004),28-joint Disease Activity Score(SMD=0.20,95%CI:0.04-0.37,P=0.02),destruction of peripheral joints(OR=2.48,95%CI:1.60-3.85,P=0.00),and corticosteroids(OR=1.91,95%CI:1.54-2.37,P=0.00)were strongly associated with the development of rheumatoid arthritis-cervical spine instability.Female and corticosteroid use were independently associated with the occurrence of rheumatoid arthritis-cervical spine instability. CONCLUSION:Based on clinical evidence from 16 observational studies,the overall incidence of rheumatoid arthritis-cervical spine instability was 43.08%.However,the incidence of cervical spine instability in rheumatoid arthritis patients varied greatly among different studies.Gender(female)and the use of corticosteroids were confirmed as independent correlation factors for the onset of cervical spine instability in patients with rheumatoid arthritis.The results of this study still provide some guidance for early clinical recognition,diagnosis,and prevention of rheumatoid arthritis-cervical spine instability.