Cognitive decline is one of the main clinical symptoms of neurodegenerative diseases. There is no specific drug treatment, which seriously affects the quality of life and rehabilitation process of these patients. Non-invasive brain stimulation (NIBS) technology such as transcranial magnetic stimulation and transcranial electrical stimulation known as its advantages of non-invasive, painless, and easy to operate, has been used in clinical treatment of cognitive disorders. In particular, it has a good effect on improving cognitive functions such as memory, attention, orientation and language ability. In recent years, the study of cerebellar involvement in learning and memory through brain-cerebellar circuit has attracted much attention, and cerebellum has become a new target for NIBS technology exploration. However, the correlation between cerebellar NIBS and cognitive function regulation is still unclear. This paper aims to provide the evidences of the anatomic and functional basis of cerebellar involvement in cognitive function regulation and cerebellar non-invasive stimulation on cognitive function regulation.

BackgroundPrevious studies have found that patients with generalized anxiety disorder （GAD） have impaired performance in executive function， and group cognitive behavioral therapy （CBT） has been shown to be effective in alleviating negative affect in patients with GAD， while its efficacy on executive function remains unclear. ObjectiveTo explore the efficacy of group CBT on anxiety symptom and executive function in GAD patients， so as to provide references for the rehabilitation program for GAD. MethodsA total of 80 consecutive patients with GAD who were hospitalized in Sleep and Psychosomatic Medical Center of Shiyan Taihe Hospital from March 2021 to August 2022 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for GAD were enrolled， and they were assigned into study group （n=40） and control group （n=40） using random number table methods. All patients were subjected to routine medication treatment and regular health education， based on this， study group received group CBT once a week （6 weeks， 60 to 90 minutes per session）. At the enrollment and after 6 weeks of treatment， patients were assessed using Hamilton Anxiety Scale （HAMA） and Frontal Assessment Battery （FAB）. ResultsANOVA with repeated measures on HAMA score revealed a significant time effect （F=1 870.320， P<0.01）， no significant group effect and no significant time×group interaction effect （F=1.254， 0.293， P>0.05）. Significant time effect， group effect and time×group interaction effect were reported on FAB scores （F=311.190， 4.399， 7.021， P<0.05 or 0.01）. Further analysis indicated that FAB scores of both groups after treatment were higher than those at baseline （t=200.569， 115.401， P<0.01）.And the FAB score of study group was higher than that of control group after treatment （t=-3.211， P<0.01）. ConclusionGroup CBT combined with medication treatment for GAD may alleviate the anxiety symptoms and improve executive function in GAD patients. ［Funded by Shiyan Science and Technology Bureau Pilot Scientific Research Project （number， 21Y21）］

Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.

Objective A scoping review of research on mobile glucose management in pregnant women with gestational diabetes mellitus was conducted to provide references for clinical providers to conduct mobile glucose management and related research.Methods Based on Arksey and O'Malley's scoping review reporting framework,JBI Library,Cochrane Library,PubMed,Web of Science,Embase,CINAHL Complete,CBM,China National Knowledge In-frastructure(CNKI),and Wanfang Database were retrieved.The search time frame was from the establishment of the databases to February 14,2023.The included literature was screened,summarized and analyzed.Results A total of 65 publications from 11 countries were included,among which 38 were randomized controlled trials,27 were experimental studies.The vehicles relied on for mobile glucose management in gestational diabetes mainly included APPs,remote monitoring systems,professional websites,and social platforms,which could provide health education,glucose management monitoring and recording,social support,and glucose management follow-up and reminders to pregnant women.Most of the studies focus on the glucose index and drug use,pregnancy outcome,self-management,quality of life,user experience and resource cost of pregnant women.Conclusion Mobile glucose management carriers are geographically specific and have a positive effect on glucose control in gestational diabetes.Future studies need to further develop localized mobile glucose management intervention protocols and conduct more high-quality randomized controlled studies to verify their effectiveness.

As cerebellum is involved in sleep regulation, cerebellar dysfunction can lead to sleep disorders, and changes in cerebellar structure and function have also been observed in some patients with sleep disorders. However, the exact mechanism of cerebellum regulation of sleep is still unified. This review summarized the anatomical basis of cerebellar neuronal activity changes with sleep-wake cycle, the changes of cerebellar and brain connection circuits during sleep-wake cycle, the abnormal behaviors caused by cerebellar function/structure disorders, and the abnormal changes of cerebellar structure in patients with different sleep disorders. It is proposed that cerebellar is involved in regulating sleep, and there are different forms of sleep disorders in patients with cerebellar dysfunction. The structural and functional integrity of cerebellum are also affected by sleep, suggesting that there may be a causal relationship between cerebellar structural and functional abnormalities and sleep disorders. Based on the high plasticity of cerebellar neurons, the electrophysiological mechanisms of cerebellar involvement in sleep may be further explored by regulating the electrical activity of cerebellar neurons in the future, so as to verify the possibility of improving sleep disorders through cerebellar regulation.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective:To investigate the effect and mechanism of the V-set and immunoglobulin domain-containing 4 ( VSIG4 ) gene mutation on the function of microglia in retinitis pigmentosa (RP). Methods:Localization of VSIG4 in the retina was detected by immunofluorescence.HMC3 cells (human microglial cells) were transfected with wild-type (Len-WT) VSIG4 gene, mutant type (Len-Mut) VSIG4 gene and empty vector virus (Len-Cont) and stimulated by the presence or absence of lipopolysaccharide (LPS), then divided into control group, LPS-Len-Mut group, LPS-Len-WT group, LPS-Len-Cont group, Len-Mut group, Len-WT group and Len-Cont group.The mRNA expression levels of the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by real-time fluorescence quantitative PCR.Protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4), nuclear transcription factor-κB (NF-κB) p65 subunit (P65), and phosphorylated P65 (PP65) were detected by Western blot.Cell phagocytic function was detected by phagocytosis assay.Cell migration ability was detected by cell scratch and transwell migration assay.LPS- stimulated HMC3 cells were co-cultured with 661W cells (mouse retinal photoreceptor cells), and the expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins of the cells were detected by Western blot.The number of apoptotic cells was determined by apoptosis assay. Results:VSIG4 was localized to microglia in mouse retina.The real-time fluorescence quantitative PCR results showed that compared with LPS-Len-WT group, the relative expression levels of IL-1β and TNF-α mRNA in HMC3 cells were significantly increased in LPS-Len-Mut group (both at P<0.05).The Western blot results showed that compared with LPS- Len-WT group, the protein expression levels of Nrf2, HO-1, and GPX4 in HMC3 cells were significantly reduced in LPS-Len-Mut group, and the PP65/P65 ratio was significantly increased (all at P<0.05).The phagocytic experiment results showed that the phagocytic rates of HMC3 cells in Len-Cont group, LPS-Len-Cont group, LPS-Len-WT group, and LPS-Len-Mut group were (35.67±3.22)%, (63.67±10.07)%, (84.00±3.46)%, and (64.67±2.31)%, respectively, showing a statistically significant difference ( F=59.06, P<0.001).Compared with LPS-Len-WT group, the phagocytic rate of HMC3 cells was significantly reduced in LPS-Len-Mut group ( P<0.05).The results of cell scratch and transwell migration assay showed that compared with LPS-Len-WT group, the migration rate of HMC3 cells at 24 and 48 hours and the number of invading cells per unit area at 24 hours were significantly reduced in LPS-Len-Mut group (all at P<0.05).Compared with LPS-Len-WT group, the expression ratio of Bax/Bcl-2 protein and the number of cell apoptosis were significantly increased in the LPS-Len-Mut group under the co-culture system (both at P<0.05). Conclusions:VSIG4 is localized to mouse retinal microglia.When the VSIG4 gene in RP mutates, HMC3 cells under LPS stimulation exhibit a series of changes, including activation of the NF-κB signaling pathway, decreased activation of the Nrf2/HO-1 signaling pathway, increased secretion of inflammatory cytokines, reduced phagocytic and migratory abilities, and increased cell apoptosis in co-culture systems.

Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.

Objective: Analyzing the characteristics of consonant errors in children with functional dysarthria in different age groups and the effect of speech training provides a reference for clinical treatment. Methods : This study followed medical ethics, and informed consent has been obtained from patients. Speech data from 388 patients with functional dysarthria were retrospectively studied. They were divided into two groups at the age of 6, namely, the preschool group (4-6 years old) of 226 patients and the school age group (6-13 years old, including 6 years old) of 162 patients. The characteristics of consonant pronunciation errors from four aspects were analyzed: average number of errors, pronunciation location, pronunciation method, and error type. One-on-one speech training was conducted, with a training frequency of once a week and once for 30 minutes. The training method was carried out in the order of phoneme training, syllable training, vocabulary training, sentence training, and short text and conversation training. The effects of speech training in the two groups were compared. Results: Analysis by pronunciation location: both age groups had the highest frequency of errors in tongue tip posterior sounds; the school age group had the lowest error frequency for labiodental consonants, and the preschool group had the lowest error frequency for bilabial consonants. According to the analysis of pronunciation mode, both age groups had the highest error frequency of aspirated affricate and the lowest error frequency of nasal sound. Analysis by error type: both age groups are mainly characterized by substitution and omission. Compared with the preschool group, most consonants of patients in the school group tend to improve in terms of pronunciation location, pronunciation mode, and error types. Compared with the preschool group, the two types of errors-palatalization and lateralization-increased in frequency in the school group, but the trend of increased lateralization was not statistically significant. After 6.7 and 5.5 sessions of speech training, the pronunciation of the preschool group and the school-age group significantly improved; the cure rate of the school-age group was 84.9% (118/139), and that of the preschool group was 77.1% (91/118). There was no statistically significant difference in the cure rate between the two groups. Conclusion Functional dysarthria may improve with age, but it may not completely self-heal. Children of different age groups can achieve good treatment results through scientific and reasonable speech training.