Objective To analyze the expression levels of serum microRNA(miR)-211 and miR-202 in patients with Alzheimer's disease and their correlation with cognitive function,anxiety and depression.Methods A total of 90 patients with Alzheimer's disease admitted to Hebei Yanda Hospital from March 2019 to March 2022 were selected as the research group.According to the Clinical Dementia Rating(CDR)score,the patients were grouped into mild group(n=24),moderate group(n=48)and severe group(n=18).Another 90 healthy individuals who underwent physical examination were collected as the control group.The expression levels of miR-211 and miR-202 in serum were compared.Pearson method and Spearman method were used to analyze serum miR-211 and miR-202 and their correlation with cognitive function,anxiety and depression.Logistic regression analysis was used to analyze the influencing factors of Alzheimer's disease.Results The expression levels of serum miR-211(0.59±0.16,1.01±0.31)and miR-202(0.35±0.10,1.00±0.32)were significantly reduced in the research group and control group,with significant differences(t=11.422,18.393,all P<0.05).Serum miR-211(0.73±0.21,0.62±0.17,0.32±0.08)expression levels,miR-202(0.51±0.15,0.33±0.10,0.19±0.04)expression levels,mini-mental state examination(MMSE)score(22.54±1.41 score,19.35±1.01 score,16.23±1.00 score)and Montreal cognitive assessment(MoCA)score(25.35±2.60 score,18.59±1.32 score,16.59±1.24 score)in the mild,moderate and severe groups gradually decreased,and the differences were statistically significant(F=32.006,46.917,163.048,163.703,all P<0.05).Compared with mild group,the serum miR-211,miR-202,MMSE and MoCA scores of severe group and moderate group were reduced,and the differences were statistically significant(t=3.685～25.375,all P<0.05).The mild,moderate and severe groups had a gradual increase in Hamilton anxiety scale(HAMA)score(12.34±1.27 score,20.59±2.09 score and 31.29±2.19 score)and Hamilton depression scale(HAMD)score(14.35±2.13 score,23.89±2.20 score and 35.35±1.21 score),and the differences were statistically significant(F=496.059,553.939,all P<0.05).According to Pearson correlation analysis,miR-211 was positively correlated with miR-202(r=0.651,P<0.05).According to Spearman correlation analysis,miR-211 and miR-202 were positively correlated with MMSE and MoCA(r=0.539～0.585,all P<0.05)and negatively correlated with HAMA and HAMD(r=-0.651～-0.539,all P<0.05).Logistic regression analysis showed that the low expression of miR-211[OR(95%CI):5.321(1.648～17.180)]and miR-202[OR(95%CI):3.158(1.989～5.012)]were risk factors for Alzheimer's disease(P<0.05).Conclusion The serum expression levels of miR-211 and miR-202 in patients with Alzheimer's disease were reduced,indicating miR-211 and miR-202 were closely related to cognitive function,anxiety and depression.

Objective:To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally.Methods:The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software.Results:DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group ( P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion:The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective To investigate the role of transcranial magnetic stimulation(TMS)in the modulation of abnormal functional status and damage characteristics of key brain regions in adult patients with anisometropic amblyopia via the resting-state functional magnetic resonance imaging(rs-fMRI)technique.Methods Single(left)eyes of 20 adult refractive amblyopia patients were included in this study and randomly divided into a surgical group[Implantable Collamer Lens(ICL)surgery]and a TMS combined group(TMS treatment on top of the surgical group),with 10 patients in each group.In both groups,the visual a-cuity of patients was examined before and after treatment via international standard visual acuity charts to evaluate the therapeu-tic effect.Moreover,patients in both groups underwent an fMRI examination once before and after treatment,and local coher-ence(ReHo),amplitude at low frequency(ALFF),and ratio amplitude at low frequency(fALFF)algorithms were used to char-acterize the functional state and response characteristics of the brain regions in the acquired f MRI images.Results Compared with that before treatment,the visual acuity of patients in both groups significantly improved after treatment and was signifi-cantly greater than the pretreatment corrected visual acuity(P＜0.05).Compared with that in the two groups after treatment,the improvement in visual acuity in the TMS combined group was greater than that in the surgical group(P＜0.05).There was no difference in the ReHo or fALFF values before and after treatment between the TMS combined group and surgical group.Compared with those before treatment,the ipsilateral frontal ALFF values were increased in the surgical group after treatment,and the ipsilateral cerebellar ALFF values were decreased in the TMS combined group.Compared with those in the surgical group,the ipsilateral frontal lobe and superior frontal gyrus ReHo values decreased,the contralateral temporal lobe and superior temporal gyrus ALFF values decreased,and the contralateral occipital lobe and cuneiform lobe fALFF values increased after treatment in the TMS combined group(all P＜0.05).Conclusion The improvement in spontaneous brain activity in pa-tients with anisometropic amblyopia in the surgical group and in the TMS combined group was significant.ICL implantation may act by activating the ipsilateral frontal lobe,ICL implantation in combination with TMS may act by improving cerebellar func-tion,increasing the excitability of the contralateral occipital and cuneate lobes,modulating neuronal activity in the adjacent cor-tex of the occipital lobe and in the other visually related cortices(ipsilateral frontal and contralateral temporal lobes),and correc-ting the difference in excitability between the two eyes of the patients.and correcting the excitability differences between the pa-tient's two eyes.

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.

Background Aluminum and fluoride are neurotoxic, and aluminum exposure alone is closely related to the overall cognitive function of operational workers. It is unclear about the effect of aluminum and fluoride interactions on cognitive function. Objective To evaluate a potential interaction effect of blood aluminum and urinary fluoride on the overall cognitive function of workers working in an aluminum plant. Methods Using cluster sampling, 230 workers in the electrolysis workshop of an aluminum group company in Shanxi Province were selected, and plasma aluminum concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) and urinary fluoride by ion-selective electrode. The study participants were divided into a low blood aluminum group and a high blood aluminum group according to the median (M) of blood aluminum concentration, and a low urinary fluoride group and a high urinary fluoride group by a predetermined cutoff point (2.160 mg·L⁻¹). The Montreal Cognitive Assessment-Beijing (MoCA-BJ) was used to assess overall cognitive function of the workers. Logistic regression model was used to analyze the relationship between blood aluminum, urinary fluoride, and mild cognitive impairment (MCI), including multiplicative interaction analysis and correlation analysis; R language was used to fit an additive interaction model of blood aluminum and urinary fluoride on MCI and to calculate synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (API). Results Among the 230 operational workers, the median blood aluminum concentration (P₂₅, P₇₅) was 40.11 (25.16, 58.89) µg·L⁻¹, and there were 104 cases of abnormal urinary fluoride, with an abnormality rate of 45.2%. There was a multiplicative interaction (OR=7.783, 95%CI: 1.377, 43.991) and no additive interaction (RERI=0.030, 95%CI: −0.498, 0.559; API=0.018, 95%CI: −0.279, 0.316; S=1.049, 95%CI: 0.519, 2.118) for the effect between blood aluminum and urinary fluoride on overall cognitive function of the workers. The logistic regression analysis showed that the risk of MCI was 12.105 (95%CI: 2.802, 52.287) times higher in workers with both high blood aluminum and high urinary fluoride than in those with low blood aluminum and low urinary fluoride, after adjusting for selected influencing factors. Conclusion Occupational exposure related high blood aluminum and high urinary fluoride are risk factors for cognitive dysfunction, and the coexistence of both indicators increases the risk of MCI in workers with occupational aluminum exposure, with a multiplicative interaction.

ObjectiveTo explore the efficacy of acupuncture intervention for children with monocular refractive-parallax amblyopia and the possible mechanisms of brain function based on resting-state functional magnetic resonance （rs-fMRI）. MethodsSeventy-six children with anisometropic amblyopia were randomly divided into routine treatment group （38 cases） and acupuncture treatment group （38 cases）. In the conventional group， the children were given three regular treatments of red flash， grating and visual stimulation for 5 mins each time； in the acupuncture group， on the basis of the conventional treatment， the children were given acupuncture for 20 mins each time on bilateral Jingming （BL 1）， Cuanzhu （BL 2）， Guangming （GB 37） and Fengchi （GB 20）； the children in both groups were treated once every other day and three times a week for 4 weeks. The corrected visual acuity was compared between groups before and after treatment. Fifteen children with left-sided refractive amblyopia were randomly selected from each of the above two groups and underwent brain rs-fMRI scans before and after treatment， and 10 healthy children with normal visual acuity of the matched gender and age were included in the normal group and underwent brain rs-fMRI scans. Based on the activation likelihood estimation （ALE） method， we constructed the what visual pathway network， and compared and analyzed the spherical regions of interest （ROIs） of the children with normal children， and both groups of children with differences in functional connectivity （FC values） within the what pathway in the brain before and after treatment. ResultsTwo cases dropout in the acupuncture group， and finally 36 cases in the acupuncture group and 38 cases in the conventional group were included in the analysis. Compared with before treatment， the best corrected visual acuity of amblyopia in both groups was significantly improved after treatment （P＜0.05）， and the improvement of vision in the acupuncture group was significantly better than that in the conventional group （P＜0.05）. The results of rs-fMRI showed that the FC values of the primary optic cortex and the right fusiform gyrus， the left lingual gyrus and the right fusiform gyrus， and the right infraoccipital gyrus and the right middle temporal gyrus were significantly elevated in the brain of the refractive amblyopia children with the whitepathic amblyopia， compared with that of the normal children （P＜0.05）. The FC values of the left lingual gyrus， the right suboccipital gyrus with the right fusiform gyrus， the left lingual gyrus with the right middle temporal gyrus， the right and left lateral middle occipital gyrus， and the right and left lateral middle occipital gyrus with the right suboccipital gyrus were significantly （P＜0.05） lower in the conventional group compared with those in the conventional group before treatment. Compared with that before acupuncture treatment， the FC values of the right lingual gyrus and the right fusiform gyrus， the primary visual cortex and the right middle temporal gyrus increased significantly after acupuncture treatment （P＜0.05）， and the FC values of the left inferior occipital gyrus and the right middle temporal gyrus， the FC values of the left lingual gyrus and the right middle occipital gyrus decreased significantly （P＜0.05）. Compared between groups after treatment， the FC between the left suboccipital gyrus and the right fusiform gyrus in the acupuncture group was significantly higher than that in the conventional group （P＜0.05）， and the FC between the left middle occipital gyrus and the right and left suboccipital gyrus was significantly lower than that in the conventional group （P＜0.05）. ConclusionAcupuncture can significantly improve the corrected vision of anisometropic amblyopic children， and its effect mechanism may focus on regulating the occipito-temporal interlobular functional connectivity within the what pathway， thus improving the children's visual function of shape and color vision and visual learning and memory ability.

Objective:To explore the effect of high intensity interval training (HIIT) on cardiac rehabilitation in patients after heart transplantation.Methods:According to the search terms, the search was conducted on China National Knowledge Infrastructure, VIP, WanFang Data, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Embase, and EBSCO. The search time limit was from the establishment of the database to January 31, 2022. After 2 researchers screened the article, extracted information, and evaluated the quality, a Meta-analysis was conducted using RevMan 5.4 software.Results:According to the inclusion and exclusion criteria, 10 English articles were selected, including 191 patients in the intervention group and 212 patients in the control group, with a total of 403 patients. Meta-analysis showed that during cardiac rehabilitation exercise in patients after heart transplantation, HIIT could improve peak oxygen uptake in cardiopulmonary function exercise testing [ MD=1.98, 95% confidence interval ( CI) (0.55, 3.41), P=0.007], peak heart rate in chronotropic responses [ MD=6.93, 95% CI (2.62, 11.24), P=0.002], and muscle exercise ability [ MD=337.18, 95% CI (12.02, 62.35), P=0.04]. There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, peak systolic blood pressure, peak diastolic blood pressure, resting heart rate and respiratory exchange rate between the two groups ( P>0.05). A subgroup analysis of peak oxygen uptake was conducted based on the intervention period and the start time of rehabilitation exercise after heart transplantation. The results showed that there were statistically significant differences in peak oxygen uptake between the intervention group and the control group when the intervention period was ≤ 12 weeks or the start time was > 6 weeks ( P<0.01) . Conclusions:HIIT effectively improves the peak oxygen uptake, peak heart rate, and muscle exercise activity of patients after heart transplantation. HIIT has a significant impact on peak oxygen uptake when the rehabilitation exercise start time after heart transplantation is > 6 weeks or the intervention period is ≤ 12 weeks.

Objective:To explore the practical role of massive open online course (MOOC) mode based on the cultivation of creativity and thinking ability in clinical human anatomy teaching.Methods:Two classes of clinical medicine students of Batch 2019 were selected in the study, and one class was control group ( n=73), which adopted the traditional teaching mode of face-to-face teaching; the other class was research group ( n=79) and the MOOC mode based on the cultivation of creativity and thinking ability for teaching was adopted. After the teaching, the students' creativity, thinking ability, self-learning ability and learning interest were compared, and the mastery of knowledge (theoretical scores and anatomical operation assessment) and satisfaction with teaching were compared between the two groups. SPSS 19.0 was used for t test, chi-square test and rank sum test. Results:The scores of creativity, thinking ability, self-study ability and learning interest of the research group were significantly higher than those of the control group after the teaching ( P<0.05). The scores of theoretical knowledge[(91.41±6.28) points] and anatomical operation[(87.41±7.25) points] in the research group were significantly higher than those in the control group after the teaching[(85.24±7.36) points and (80.26±6.38) points] ( P<0.05). There was significant difference in the distribution of teaching satisfaction between the two groups ( P<0.05), and the total satisfaction rate for teaching of the research group (94.94%) was higher than that of the control group (83.56%). Conclusion:The MOOC mode based on the cultivation of creativity and thinking ability in clinical human anatomy teaching can significantly improve students' creativity, thinking ability and self-learning ability, improve their learning interest and mastery of human anatomy knowledge, and improve their satisfaction with teaching.