After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C₁₈（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

Objective:To preliminarily explore the long-term improvement of low-frequency deep brain stimulation (DBS) on the nucleus basalis of Meynert (NBM) in cognitive disorders, neuropsychiatric symptoms and sleep disorders of patients with early-onset severe Alzheimer's disease (AD).Methods:A retrospective study was performed; 18 patients with early-onset severe AD admitted to Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2016 to December 2022 were included. These patients were divided into NBM-DBS group and control group according to different treatments; 6 patients received low-frequency NBM-DBS on basis of conservative treatments; 12 patients accepted conservative treatments. Changes in Brief Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Hamilton Depression Rating Scale (HAMD), Becker-Lavanson Mania Scale (BRMS), Pittsburgh Sleep Quality Index (PSQI), and Zarit Caregiver Burden Interview (ZBI) were observed before treatment and 1 year after follow up.Results:MMSE and MoCA scores 1 year after follow up obviously reduced compared with those before treatment in both NBM-DBS and control patients; MMSE and MoCA scores in NBM-DBS patients showed no significant differences between 1 year after follow up and before treatment ( P>0.05), while significant differences were noted in the control group between 1 year after follow-up and before treatment ( P<0.05); and no significant differences in MMSE and MoCA scores were noted between the 2 groups 1 year after follow up ( P>0.05). NPI, HAMD, BRMS and ZBI scores in the NBM-DBS group 1 year after follow up were significantly different compared with those before treatment ( P<0.05); no significant differences were noted in NPI, HAMD and ZBI scores in the control group between 1 year after follow up and before treatment ( P>0.05), while significant difference was noted in BRMS scores ( P<0.05); significant differences in NPI, HAMD, BRMS and ZBI scores were noted between the 2 groups 1 year after follow up ( P<0.05). Conclusion:Low-frequency NBM-DBS is not only effective in improving cognitive disorders, but also effective in improving neuropsychiatric symptoms and sleep disorders, as well as reducing caregiver burden in patients with early-onset severe AD.

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E^-∕- （ApoE^-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE^-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg^-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE^-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

Objective To investigate the effect of hairy and enhancer of split 5(HES5)on transdifferentiation and apoptosis of renal tubular epithelial cells induced by TGF-β1 and its potential mechanism.Methods The differentially expressed genes in GSE66494 data were analyzed and screened.The mouse model of unilateral uretera obstruction(UUO)was established,and the expression level of HES5 was detected in the renal tissue.HK-2 cells were treated with 10 ng/mL TGF-β1 for 24 h to establish a tubular epithelial-mesenchymal transition(EMT)model,and then qRT-PCR and Western blotting were performed to detect the expression of HES5 at mRNA and protein levels.After HK-2 cells were transfected with the plasmid overexpressing HES5,the protein levels of fibronectin,collagen Ⅰ,vimentin,apoptosis markers Bax and Bcl2 were detected in 24 h later.Then,HK-2 cells were divided into Control group,siHES5 group,TGF-β 1 group,and siHES5+TGF-β1 group.The protein level of fibrosis and apoptosis markers were measured in above groups with Western blotting.TUNEL staining and flow cytometry were employed to detect cell apoptosis.Western blotting was applied to determine the protein levels of AKT,p-AKT,PI3K and p-PI3K.HK-2 cells overexpressing HES5 were treated with PI3K inhibitor LY294002,and the expression of vimentin was detected.Results The expression of HES5 was significantly up-regulated in both chronic kidney disease(CKD)and fibrotic kidneys of mice.Overexpression of HES5 promoted the synthesis of fibronectin,collagen Ⅰ,vimentin and Bax in HK-2 cells,and inhibited the expression of Bcl2(P＜0.05).HES5 knockdown not only down-regulated the expression of fibrosis markers,but also inhibited the apoptosis of HK-2 cells.Furthermore,HES5 knockdown inhibited the activation of PI3K/AKT signaling pathway induced by TGF-β1 in HK-2 cells(P＜0.05).Inhibitors of the PI3K/AKT signaling pathway inhibitor attenuated the induction of HES5 on vimentin.Conclusion HES5 knockdown inhibits the transdifferentiation and apoptosis in TGF-β1-induced renal tubular epithelial cells,which may be related to the decreased activity of the PI3K/AKT signaling pathway.

Objective:To establish the QAMS method for content determination of eight chemical compositions (chlorogenic acid, neochlorogenic acid, cryptochlorogenin acid, isochlorogenic acid A, isochlorogenic acid C, rutin, morroniside and luteolin-7-O-glucoside) from Lonicera alberti Regel. leaves; To verify the feasibility and applicability of this method in quality control for Lonicera alberti Regel. leaves. Methods:The HPLC analysis was performed on a Agilent Eclipse XDB-C18 (250 mm×4.6 mm,5 μm) with a mobile phase consisted of acetonitrile and 0.1% formic acid solution in gradient elution manner at a flow rate of 1 ml/min. The column temperature was maintained at 30 ℃ and the detection wavelength was set at 258 nm. The injection volume was 10 μl.Results:Chlorogenic acid, neochlorogenic acid, cryptochlorogenin acid, isochlorogenic acid A, isochlorogenic acid C, rutin, morroniside and luteolin-7-O-glucoside had a good linear relationship in the corresponding concentration range ( r≥0.999 6). The average sample recovery rates were 103.16%, 103.98%, 99.49%, 103.78%, 102.74%, 101.12%, 104.62%, and 100.94%, respectively. The RSD values were 1.30%, 1.63%, 2.92%, 2.10%, 1.27%, 2.40%, 1.15%, and 2.76%, respectively. Chlorogenic acid was set as internal reference substance, the relative correction factors of isochlorogenic acid A, isochlorogenic acid C, neochlorogenic acid, cryptochlorogenin acid, morroniside, luteolin-7-O-glucoside, rutin were 0.785 5, 0.693 9, 1.001 5, 1.087 2, 1.233 9, 0.369 1, 0.507 5, respectively. The content determination results of QAMS method and external standard method showed that there was no statistical significance in the comparison of the other six components except for morroniside. Conclusions:The established HPLC method can be used for the quality control of Lonicera alberti Regel. leaves. QAMS can be used to determine the contents of neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, rutin and luteolin-7-O-glucoside in Lonicera alberti Regel. leaves.

Objective:A scoping review of factors influencing eHealth literacy in older adults to inform future research and clinical practice.Methods:Accordance with the scope review methodological framework, research questions were established, and PubMed, Web of Science, Medline, CINAHL, Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP databases were systematically searched for the timeframe of the search from the time the database was constructed to November 24, 2023.Results:A total of 29 articles were included in the literature, which met the criteria of inclusion exclusion. The main factors influencing eHealth literacy among older adults included sociodemographic factors, disease-related factors, Internet use characteristics, psychosocial factors, healthy aging, and perceived health risks.Conclusions:eHealth literacy in older adults is affected by many complex factors. Most of the measurement tools are universal scales, and there are differences in the results of studies in different groups and regions. Future studies may consider using or developing specific eHealth literacy assessment tools for older adults, and carrying out targeted studies on older adults with different group characteristics.