ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective:To investigate the effect of Early infarct growth rate(EIGR) on the prognosis of patients with acute large vessel occlusive ischemic stroke.Methods:A total of 164 patients with acute large vessel occlusive ischemic stroke were enrolled in the emergency department of the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to December 31, 2022.According to the change of the National Institutes of Health Stroke Scale (NIHSS) score at admission and 72 h after treatment, the patients were divided into good prognosis group and poor prognosis group. The basic clinical data of the two groups were observed and compared. The risk factors of poor prognosis were analyzed by univariate regression. The effect of EIGR on prognosis after age stratification was further analyzed.Results:Comparing the clinical data of the two groups, there was no difference in EIGR (mL/h) (7.67 vs. 8.24, P=0.211) between the two groups. The product between EIGR and age was included as the interaction term, and the result of the interaction term in the model was statistically significant ( OR=1.002, 95% CI: 1.000-1.003, P=0.032) .Moreover, the result was still statistically significant after adjusting for relevant variables (gender, history of hypertension, history of atrial fibrillation, history of diabetes, history of coronary heart disease, and history of stroke) ( OR=1.002, 95% CI:1.000-1.003, P=0.027). Subgroup analysis was performed according to the median age (71 years). In the elderly group, the proportion of poor prognosis was higher with fast core infarction growth rate defined by 25 mL/h and 15 mL/h ( P < 0.05).In the younger age group, there was no significant difference in the proportion of poor prognosis in the fast core infarction growth rate compared with the slow type ( P > 0.05). Conclusions:EIGR can predict the early clinical outcome early in elderly patients with large vessel occlusive ischemic stroke.

Mayaro fever is a mosquito-borne viral infectious disease caused by Mayaro virus (MAYV). The main clinical symptoms are sudden onset of high fever triad, arthralgia and maculopapular rash. MAYV outbreaks occur more frequently in the Americas Region, particularly within tropical forests in Brazil. However, in recent years, virus circulation has been spreading to the Switzerland and Netherlands in Europe, which may invade urban areas and cause epidemics across the region. Consequently, this work focuses on the epidemiological characteristics and research progress of MAYV prevention and control, including biological characteristics, epidemiology, transmission vectors, prevention measures and treatment of this virus.

AIM To investigate the clinical effects of Modified Shugan Qingzhi Decoction on patients with type 2 diabetes mellitus complicated with dyslipidemia.METHODS One hundred and sixty patients were randomly assigned into control group(80 cases)for 8-week intervention of conventional treatment,and observation group(80 cases)for 8-week intervention of both Shugan Qingzhi Decoction and conventional treatment.The changes in clinical effects,lipid metabolism indices(TC,TG,LDL-C,HDL-C,Chemerin,ApoA1,ApoB,LPa),glucose metabolism indices(FBG,2 hPG,HbA1c),irisin,food ingestion inhibitor-1,TCM syndrome scores and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased HDL-C,irisin(P＜0.05),and decreased TC,TG,LDL-C,Chemerin,ApoA1,ApoB,LPa,glucose metabolism indices,food ingestion inhibitor-1,TCM syndrome scores(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with type 2 diabetes mellitus complicated with dyslipidemia,Modified Shugan Qingzhi Decoction can safely and effectively regulate glucose and lipid metabolism and levels of irisin,feeding inhibition factor-1,Chemerin.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Takayasu arteritis is a chronic inflammation involving large vessels and it often occurs in young women of childbearing age. We described a case of a 29- year- old lady with previous history of proliferative ischemic retinopathy was noted to have low upper limbs blood pressure and weak upper limb pulses postpartumly. An urgent CT angiogram of thorax revealed features suggestive of large vessel vasculitis with involvement of ascending arch, descending aorta and its main branches, corresponding to type II TA . She was diagnosed to have Takayasu arteritis post delivery, and she underwent a successful pregnancy without intrapartum and postpartum complications. High index of suspicion must be given for pregnant patient who have persistent low blood pressure and weak pulse for early detection to avoid severe complications.

OBJECTIVE: To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats. METHODS: Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E₂, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E₂, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E₂) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting. RESULTS: Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05). CONCLUSION KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.
Female ; Rats ; Animals ; Humans ; Angiotensin II ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Hypertension/drug therapy* ; Estradiol/pharmacology* ; Superoxide Dismutase ; Ovariectomy ; Mammals/metabolism*

Objective:To investigate the expressions of Nod-like receptor protein 3 (NLRP3), cysteine-aspartic acid protease 1 (Caspase-1), and Gasdermin D (GSDMD) in nasopharyngeal carcinoma (NPC), and their relationships with the recurrence and metastasis of NPC.Methods:A retrospective study was conducted on 421 patients diagnosed with NPC between December 2014 and January 2020. The expressions of NLRP3, Caspase-1, and GSDMD in pathological specimens were examined with immunohistochemistry and multiplex immunofluorescence staining. Univariate and multivariate Cox regression analyses were applied to identify the factors influencing NPC recurrence and metastasis. In vitro experiments with NPC cell line HNE-2 were used to explore the functional mechanisms of NLRP3, Caspase-1, and GSDMD.Results:Multivariate Cox analysis revealed that tumor staging of Ⅲ-Ⅳ( HRrecurrence=2.74, 95% CIrecurrence: 1.61-4.65; HRmetastasis=1.90, 95% CImetastasis: 1.04-3.49) and pre-treatment plasma EBV-DNA levels≥1 500 copies/ml ( HRrecurrence=1.91, 95% CIrecurrence: 1.13-3.23; HRmetastasis=2.07, 95% CImetastasis: 1.23-3.50)were independent risk factors for NPC recurrence and metastasis, while positive expression of NLRP3( HRrecurrence=0.17, 95% CIrecurrence: 0.08-0.35; HRmetastasis=0.30, 95% CImetastasis: 0.15-0.59), Caspase-1( HRrecurrence=0.32, 95% CIrecurrence: 0.18-0.59; HRmetastasis=0.43, 95% CImetastasis: 0.25-0.76), and GSDMD( HRrecurrence=0.48, 95% CIrecurrence: 0.25-0.91; HRmetastasis=0.96, 95% CImetastasis: 0.53-1.74) served as independent protective factors. Age ( HR=1.02, 95% CI: 1.01-1.04) and intensity-modulated radiotherapy ( HR=0.51, 95% CI: 0.30-0.88) were independent factors for NPC recurrence, whereas chemotherapy ( HR=0.50, 95% CI: 0.29-0.88) acted as an independent protective factor for NPC metastasis (all P<0.05). NPC patients with positive expressions of the three proteins had higher locoregional recurrence-free survival, distant metastasis-free survival, and overall survival compared to those with negative expressions (all P<0.05). In vitro experiments revealed that the overexpression of NLRP3 activated the NLRP3/Caspase-1/GSDMD signaling pathway, as evidenced by Western Blot analysis. Enzyme-linked immunosorbent assay and scanning electron microscopy demonstrated that overexpression of NLRP3 promoted pyroptosis in HNE-2 cells. Cellular functional assays further confirmed that overexpression of NLRP3 significantly inhibited the proliferation, invasion, and migration of HNE-2 cells. Conclusion:Positive expressions of NLRP3, Caspase-1, and GSDMD serves as independent protective factors for recurrence and metastasis of NPC, potentially by promoting cell pyroptosis and thus inhibiting NPC cell proliferation, invasion, and migration.

OBJECTIVES: To study the etiology and clinical features of children with ascites, so as to provide a basis for the diagnosis and treatment of ascites in children. METHODS: The medical data of the children with ascites, who were hospitalized from January 1, 2010 to December 31, 2019, were retrospectively reviewed. RESULTS: Among the 165 children with ascites, the male/female ratio was 1.53:1, and the mean age of onset was (6±4) years. The causes of ascites included surgical acute abdomen (39 children, 23.6%), infectious diseases (39 children, 23.6%), neoplastic diseases (27 children, 16.4%), hepatogenic diseases (18 children, 10.9%), pancreatitis (10 children, 6.1%), cardiogenic diseases (8 children, 4.8%), rheumatic immune diseases (6 children, 3.6%), and nephrogenic diseases (5 children, 3.0%). According to the age of onset, there were 33 infants, 24 young children, 30 preschool children, 41 school-aged children, and 37 adolescents. Surgical acute abdomen and hepatogenic diseases were the main causes of ascites in infants (P<0.05). Neoplastic disease was the leading cause in young children (P<0.05). Infectious diseases were the most common cause in adolescents (P<0.05). CONCLUSIONS Surgical acute abdomen, infectious diseases, neoplastic diseases, and hepatogenic diseases are the common causes of ascites in children, and there are some differences in the leading cause of ascites between different age groups.
Abdomen, Acute/complications* ; Adolescent ; Ascites/etiology* ; Child ; Child, Preschool ; Communicable Diseases ; Female ; Humans ; Infant ; Male ; Neoplasms/complications* ; Pancreatitis/complications* ; Retrospective Studies

Humans ; Thyroid Cancer, Papillary ; Carcinoma, Papillary/surgery* ; Thyroid Neoplasms/surgery*