ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg^-1·d^-1）， and a risperidone group （2 mg·kg^-1·d^-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS⁺/ionized calcium-binding adapter molecule 1 （Iba1）⁺ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.

ObjectiveTo investigate the ameliorative effects of quercetin on neuropsychiatric symptoms associated with vascular dementia （VaD） and to elucidate the molecular mechanism， specifically whether quercetin inhibits pro-inflammatory activation of microglia by modulation of the receptor-interacting serine/threonine-protein kinase 1 （RIPK1）/NOD-like receptor protein 3 （NLRP3）/Caspase-1 signaling pathway， thereby promoting myelin repair in the medial prefrontal cortex （mPFC）. MethodsA C57BL/6J mouse model of VaD with neuropsychiatric symptoms was established by bilateral common carotid artery stenosis （BCAS） combined with chronic restraint stress （CRS）. Mice were randomly divided into a sham group， a model group， low-dose， medium-dose， and high-dose quercetin groups （30， 60， 120 mg·kg^-1·d^-1）， and a fluoxetine group （10 mg·kg^-1·d^-1）. After intervention， depressive- and anxiety-like behaviors were assessed by the sucrose preference test （SPT）， forced swim test （FST）， open field test （OFT）， and elevated plus maze （EPM）. mPFC tissue was collected. Immunofluorescence （IF） was used to detect myelin basic protein （MBP） expression and microglial morphology. Western blot was used to measure the protein level of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， inducible nitric oxide synthase （iNOS）， CD86， RIPK1， phosphorylated RIPK1 （Ser166）， NLRP3， and Caspase-1. Enzyme-linked immunosorbent assay （ELISA） was used to determine the level of tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. ResultsCompared with the sham group， the model group exhibited significant depressive- and anxiety-like behaviors （P<0.01）， significantly decreased protein expression of MBP， MOG， and MAG in the mPFC （P<0.01）， activated microglia （characterized by enlarged cell bodies， reduced protrusions， and upregulated iNOS and CD86 expressions， P<0.01）， and significantly elevated p-RIPK1/RIPK1 ratio， NLRP3， Caspase-1 protein expression， and level of TNF-α， IL-6， and IL-1β （P<0.01， P<0.05）. Compared with the model group， the quercetin treatment （especially at medium and high doses） significantly ameliorated these behavioral abnormalities （P<0.05， P<0.01）， increased the expression of MBP （protein and fluorescence intensity）， MOG， and MAG in the mPFC （P<0.05， P<0.01）， suppressed excessive microglial activation （characterized decreased cell bodies， increased protrusions， and downregulated iNOS and CD86 expressions， P<0.01）， and significantly reduced the p-RIPK1/RIPK1 ratio， NLRP3， Caspase-1 protein expression， and inflammatory cytokine levels （P<0.01）. ConclusionQuercetin effectively alleviates neuropsychiatric symptoms in VaD mice. Its mechanism may be associated with the inhibition of microglial inflammatory activation mediated by the RIPK1/NLRP3/Caspase-1 signaling pathway， thereby promoting myelin repair in the mPFC region.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.

Objective:To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China.Methods:The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed.Results:From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age.Conclusion:From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Objective:To evaluate the role of hippocampal prostaglandin-endoperoxide synthase 2 (PTGS2) in baicalin-induced reduction of cognitive dysfunction after cerebral ischemia-reperfusion injury (CIRI) in mice.Methods:Thirty healthy male C57BL/6 mice, aged 16 weeks, weighing 20-25 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (C group), CIRI group, baicalin+ CIRI group (B+ CIRI group), overexpression of PTGS2+ CIRI group (PTGS2+ CIRI group), and overexpression of PTGS2+ baicalin+ CIRI group (PTGS2+ B+ CIRI). In B+ CIRI group and PTGS2+ B+ CIRI group, baicalin-liposome 0.2 ml was injected through the tail vein, and the CIRI model was established 1 week later. In PTGS2+ CIRI group and PTGS2+ B+ CIRI group, PTGS2-overexpressed adeno-associated virus 1.2 μl was injected into the hippocampus, and the CIRI model was established 4 weeks later. CIRI model was established by using the transient (50 min) bilateral common carotid artery occlusion/reperfusion. On the 12th day after developing the model, the spatial learning and memory ability was evaluated using Morris water maze test. The expression of PTGS2 in the hippocampus was detected by Western blot, and the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6, Iba-1 and CD68 mRNA in the hippocampus was detected by quantitative real-time polymerase chain reaction. Results:Compared with C group, the escape latency was significantly prolonged, the time spent in the target quadrant was shortened, the number of crossing the original platform was reduced, and the expression of PTGS2 and expression of Iba-1, CD68, TNF-α, IL-1β and IL-6 mRNA in the hippocampus was up-regulated in CIRI group ( P<0.05). Compared with CIRI group, the escape latency was significantly shortened, the time spent in the target quadrant was prolonged, the number of crossing the original platform was increased, and the expression of PTGS2 and expression of Iba-1, CD68, TNF-α, IL-1β and IL-6 mRNA in the hippocampus was down-regulated in B+ CIRI group, and the escape latency was significantly prolonged, the time spent in the target quadrant was shortened, the number of crossing the original platform was reduced, and the expression of PTGS2 and expression of Iba-1, CD68, TNF-α, IL-1β and IL-6 mRNA in the hippocampus was up-regulated in PTGS2+ CIRI group ( P<0.05). Compared with B+ CIRI group, the escape latency was significantly prolonged, the time spent in the target quadrant was shortened, the number of crossing the original platform was reduced, and the expression of PTGS2 and expression of Iba-1, CD68, TNF-α, IL-1β and IL-6 mRNA in the hippocampus was up-regulated in PTGS2+ B+ CIRI group ( P<0.05). Conclusions:The mechanism by which baicalin attenuates cognitive dysfunction after CIRI is related to down-regulation of hippocampal PTGS2 expression and inhibition of neuroinflammation in mice.

Objective:To investigate the correlation between state-trait anxiety levels and quality of life before and after orthognathic surgery in patients with dentofacial deformities, and explore the feasibility of using the state-trait anxiety inventory(STAI) to screen postoperative patients with low quality of life.Methods:Patients with dentofacial deformities who underwent orthognathic surgery in Peking University Stomatological Hospital from September 2019 to March 2021 were selected as the research objects. STAI [including state anxiety inventory(SAI) and trait anxiety inventory(TAI)] and orthognathic quality of life questionnaire(OQLQ) were used to investigate patients before surgery, 2 weeks after surgery, 3 months after surgery and 6 months after surgery. The total scores of SAI and TAI ranged from 20 to 80 points, with higher scores implying a higher level of state-trait anxiety. The OQLQ includes four dimensions: social function, facial aesthetics, oral function and aesthetic perception, with total scores ranging from 22 to 88, higher scores representing a lower life quality level. SPSS 26.0 software used for statistical analysis, the measurement data was expressed as Mean±SD. Repeated measures ANOVA and the Bonferroni method were used to compare the SAI, TAI and OQLQ scores in different periods. Pearson correlation analysis was used to explore the correlation between patients’ demographic characteristics (gender, age, diagnostic classification, education, number of social contacts) and state-trait anxiety level, and life quality level at different periods, as well as the correlation between the state-trait anxiety level and the life quality level over time. Receiver operator characteristic(ROC) curve analysis was used to explore the feasibility of using the preoperative STAI scale to screen postoperative patients with low quality of life.Results:A total of 96 patients were included in this study, including 26 males and 70 females, aged (26.0±5.8) years. The SAI, TAI, and OQLQ total scores decreased during three postoperative periods compared to preoperative period ( P<0.01), indicating that the patients’ postoperative state-trait anxiety level decreased and their life quality level improved after surgery. Pearson correlation analysis showed a negative correlation between the patient’s social contact number and their SAI and TAI scores at postoperative 2 weeks (SAI: r=-0.30, P=0.003; TAI: r=-0.35, P<0.001). SAI and TAI scores were positively correlated in different periods ( r=0.48-0.84, P<0.01). Preoperative SAI scores and TAI scores were correlated with preoperative social function, aesthetic perception, facial aesthetic scores and total OQLQ scores (SAI: r=0.39-0.52, P<0.01; TAI: r=0.32-0.51, P<0.01). Preoperative SAI scores were positively correlated with social function and aesthetic perception scores and total OQLQ scores at 2 weeks postoperatively and with aesthetic perception, social function at 6 months postoperatively ( r=0.20-0.52, P<0.05 or <0.01). Postoperative SAI scores were positively correlated with OQLQ scores in all dimensions and total scores except for oral function scores at 3 months postoperatively, which were not correlated with the same period ( r= 0.24-0.55, P<0.05 or <0.01). Preoperative TAI scores were positively correlated with social function scores at 2 weeks( r=0.36, P<0.001) and 3 months( r=0.21, P=0.041) postoperatively. Postoperative TAI scores were positively correlated with OQLQ scores in all dimensions and total scores except for oral function scores at 2 weeks postoperatively, which were not correlated with oral function scores at the same period ( r=0.21-0.58, P<0.05 or <0.01). ROC curve analysis showed that preoperative SAI scores >34.5 and >33.5 screened people with low life quality level at postoperative 3 months and 6 months, with an area under the curve (AUC) of 0.75 (95% CI: 0.62-0.87, P=0.001) and 0.71 (95% CI: 0.59-0.84, P=0.003), respectively. Preoperative TAI scores >43.5, >42.5 and >33.5 can screen patients with low quality of life at 2 weeks, 3 months and 6 months after surgery, with AUC of 0.64(95% CI: 0.52-0.75, P=0.046), 0.73(95% CI: 0.60-0.85, P=0.001)and 0.67(95% CI: 0.55-0.80, P=0.016)respectively. Conclusion:The preoperative and postoperative state-trait anxiety level of patients with dentofacial deformity is correlated with the overall level of quality of life, social function, aesthetic perception and facial aesthetics. The preoperative application of STAI scale can screen patients with low quality of life after orthognathic surgery.