Objective To investigate the efficacy and safety of sacubitril valsartan in the treatment of heart failure(HF)of midrange ejection fraction(HFmrEF)in patients after acute myocardial infarction(AMI).Methods A total of 102 patients with HFmrEF after AMI were divided into the control group and the experimental group,with 51 cases in each group.The control group was given conventional treatment for AMI and anti-HF treatment,and the angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)was used without contraindications.The experimental group was replaced by ACEI/ARB with sacubitril valsartan on the basis of the control group.After 6 months of treatment,the total effective rates of the two groups after treatment were analyzed,and the cardiac function,N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum inflammatory factor C-reactive protein(CRP)were compared before and after treatment.The occurrence of adverse reactions after treatment was recorded.Kaplan-Meier method was used to analyze the cumulative cardiovascular mortality,HF rehospitalization rate and end-event-free survival after 6 months of treatment in two groups.Results After treatment,there was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).The total effective rate was higher in the experimental group than that of the control group(P<0.05).Compared with before treatment,left ventricular ejection fraction(LVEF),stroke volume(SV),mitral diastolic blood flow velocity E peak and A peak ratio(E/A)and 6 min walking distance(6MWD)were increased in the two groups,and left ventricular end-diastolic diameter(LVEDD)and left atrial diameter(LAD)were decreased in the two groups after treatment(all P<0.05).After treatment,LVEF,SV,E/A and 6MWD were higher in the experimental group than those in the control group(P<0.05).LVEDD and LAD were lower than those in the control group(all P<0.05).Compared with results before treatment,NT-proBNP and CRP were decreased after treatment in the experiment group than those in the control group(P<0.05).There was no significant difference in the cumulative cardiovascular mortality between the experiment group and the control group(3.9％vs.5.9％,P=0.524).The cumulative HF rehospitalization rate was lower in the experimental group than that of the control group(9.8％vs.23.5％,P=0.042).The cumulative end-point-free survival rate was higher in the experiment group than that of the control group(86.3％vs.70.6％,P=0.037).Conclusion Sacubitril valsartan is safer and more effective than ACEI/ARB in the treatment of AMI patients with HFmrEF,and it is worthy of clinical promotion.

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

The mortality rate of septic shock in children is high，and the number of cases has been increasing year by year.In recent years，the number of deaths has decreased with the development of medical technology.With the increasing number of surviving children with septic shock，the prognosis regarding these patients is gaining more attention of PICU physicians than before.The long-term sequelae of patients with septic shock，which often leads to multiple organ dysfunction and complications，severely affects the quality of children life after discharge from the hospital.Notably，the meaningful outcomes mainly include physical，mental，emotional，and social functioning.Currently，few studies focusing on quality of life in children surviving from septic shock have been reported in China.Herein，this review summarized the progress of research on the long-term prognosis of patients with septic shock.

Objective: To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced (LPS-induced) depression mouse model. Methods: We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections. The mice were divided into the following groups: control, model, fluoxetine, Tiansi Yin, Sini powder, and low-, medium-, and high-dose Peiyuan Jieyu formula groups. Forced swim and tail suspension tests were used to assess the efficacy of the depression (despair) model, and weight gain rates were also measured. Furthermore, serum levels of various depression and inflammation-associated molecules, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), tryptophan, 5-hydroxytryptamine, kynurenine (KYN), and kynurenic acid (KA) were assessed. Furthermore, the expression levels of ionic calcium-binding adaptor molecule-1 (IBA-1) and indoleamine 2,3-dioxygenase (IDO) mRNA in hippocampal microglia were measured. Results: The model group displayed greater despair-associated immobility, which was shortened in response to various doses of Peiyuan Jieyu formula. Furthermore, formula administration significantly reduced serum TNF-α levels and hippocampal IDO mRNA expression. The high formula dose also reduced IFN-γ and IBA-1 levels, the latter was also decreased in response to the medium formula dose. However, the low formula dose reduced serum KYN level and KYN/tryptophan (TRP) and KYN/KA ratios. Conclusion The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model, potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Objective:To explore the clinical characteristics, pathological features, and diagnosis and treatment strategies of nasal chondromesenchymal hamartoma (NCMH) in infants and young children.Methods:A retrospective analysis was conducted on seven cases of NCMH infants and young children admitted to Beijing Children′s Hospital, Capital Medical University from April 2015 to January 2022. The cohort included 5 males and 2 females, aged from 6 days to 2 years and 3 months. General information, clinical symptoms, imaging findings, treatment plans, postoperative complications, recurrence and follow-up time were collected, summarized and analyzed. Additionally, immunohistochemical characteristics of the lesion were examined.Results:The clinical symptoms of 7 children included nasal congestion, runny nose, open mouth breathing, snoring during sleep, difficulty feeding, and strabismus. All patients underwent electronic nasopharyngoscopy examination, with 5 cases of tumors located in the right nasal cavity and 2 cases in the left nasal cavity. No case of bilateral nasal cavity disease was found. All 7 patients underwent complete imaging examinations, with 5 patients underwent MRI and CT examinations, 1 patient underwent CT examination only, and 1 patient underwent MRI examination only. The CT results showed that all tumors were broad-based, with uneven density, multiple calcifications and bone remodeling, and some exhibited multiple cystic components. The MRI results showed that the tumor showed low signal on T1 weighted imaging and high or slightly high signal on T2 weighted imaging. All patients were diagnosed through histopathological examination and immunohistochemistry, including 7 cases of Ki-67 and SMA (+), 5 cases of S-100 and Vimentin (+), and all EMA and GFAP were negative. All patients underwent endoscopic resection surgery through the nasal approach, with 3 cases using navigation technology. Five cases of tumors were completely removed, and two cases of tumors were mostly removed. No nasal packing was performed after surgery, and no postoperative nasal, ocular, or intracranial complication occurred in all patients. Follow up assessments conducted 6 to 84 months post-surgery revealed no instances of tumor recurrence in any of the patients.Conclusions:The clinical symptoms of children with NCHM mainly depend on the size and location of the tumor. Nasal endoscopic surgery is the main treatment method. In cases where critical structures like the skull base or orbit are implicated, staged surgical interventions may be warranted. Long-term follow-up is strongly advised to monitor for any potential recurrence or complications.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.

Objective To explore the safety and feasibility of a modified superior mesenteric artery(SMA)approach in totally laparoscopic complete mesocolic excision(CME)and D3 lymphadenectomy for right colon cancer.Methods A retrospective analysis was performed on clinical data of 77 cases of totally laparoscopic radical surgery for right colon cancer from April 2021 to April 2023.Before August 2022,42 cases underwent traditional SMA approach(control group,only marking with the ileocolic vascular pedicle as the tail of SMA),while after August 2022,35 cases underwent modified SMA approach(modified group,marking with the Treitz's ligament and ileocolic vascular pedicle as the head and tail of SMA,respectively).There was no statistically significant difference in general information between the two groups(P>0.05).The intraoperative conditions,postoperative recovery,and postoperative complications were compared between the two groups.Results Compared with the control group,the modified group had a shorter surgical time[(147.3±35.8)min vs.(173.4±29.9)min,t =-3.428,P =0.001].There were no statistically significant differences in the number of lymph node dissection,number of positive lymph nodes,drainage volume,exhaust time,postoperative hospital stay,and incidence of complications between the two groups(P>0.05).Conclusion The modified SMA approach for totally laparoscopic radical resection of right colon cancer shortens the surgical time,reduces the difficulty and risk of surgery,and has high safety and feasibility.

Objective:To explore effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on macrophage M1/M2 polarization.Methods:hUC-MSCs were co-cultured with pTHP-1 cells which were macrophage-like cells induced by PMA and tran-scriptome sequencing data were analyzed.Differentially expressed genes were screened and analyzed by GO and KEGG enrichment analysis.Effect of hUC-MSCs on pTHP-1 cells proliferation was analyzed by cell proliferation assay(CCK-8 and EdU).Flow cytometry was used to verify influence of hUC-MSCs on relative contents of inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in pTHP-1 cells which were interaction with LPS.Effect of hUC-MSCs on M1/M2-related molecular phenotype of pTHP-1 cells was studied by qRT-PCR and flow cytometry.Results:Transcriptome sequencing data analysis showed that M1-related genes TNF-α(P<0.05)and HLA-DRA(P<0.01)decreased to a great extent and M2-related gene ARG1(P<0.05)increased to a great extent in pTHP-1 cells after co-culture with hUC-MSCs,suggesting that hUC-MSCs inhibited macrophage M1 polarization.GO and KEGG analysis showed that these dysregulated genes regulated inflammation and immune response.hUC-MSCs inhibited proliferation of pTHP-1 cells,reduced content of TNF-α and increased content of IL-10(P<0.001).qRT-PCR and flow cytometry showed mRNA expressions of HLA-DRA(P<0.05)and CD68(P<0.01)and CD14+CD11c+M1 macrophage percentage were down-regulated,while mRNA expressions of CD163(P<0.001),CD206(P<0.001)and CD14+CD163+M2 macrophage percentage were significantly up-regulated in pTHP-1 cells after co-culture with hUC-MSCs.Conclusion:hUC-MSCs inhibit macrophage polarization to M1 and promote polariza-tion to M2 in vitro.

Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2