Objective:To determine the effect of gastrodin(GAS)on toll-like receptor 4(TLR4)expression in mi-croglia after hypoxic-ischemic brain damage.Methods:Hypoxia-ischemic brain damage(HIBD)model was established in neonatal rat in vivo.Thirty 3 d SD rats of were randomly divided into there groups:Sham group,HIBD model group,HIBD model+gastrodin intervention group(HIBD+G).Oxygen glucose deprivation(OGD)model was established in BV2 cells in vitro,Control group(Control),oxygen glucose deprivation group(OGD),OGD+gastrodin intervention group(OGD+G)were randomly set in vitro.Both Western Blot and immunofluorescence staining techniques were used to detect the expression of TLR4 in cells of each group in vitro and in the left corpus callosum region in vivo.Results:The expression of TLR4 was significantly increased in OGD-induced microglia.After gastrodin intervention,TLR4 expression was decreased significantly(P＜0.05).Conclusion:GAS can inhibit the expression of TLR4 in activated microglia and thus play a neuroprotective role in HIBD.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.

Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95％CI:1.532～2.499),length of ICU stay (P=0.000,OR=2.561,95％CI:1.728～3.794),number of operations (P=0.015,OR=1.814,95％CI:1.124～2.927),spinal fixation (P=0.004,OR=0.370,95％CI:0.189～0.724),restrictive position (P=0.000,OR=21.269,95％CI:5.276～85.740),platelet count (P=0.000,OR=1.553,95％CI:1.236～1.951),D-dimer level (P=0.000,OR=1.600,95％CI:1.376～1.860)and prothrombin time (P=0.025,OR=2.756,95％CI:1.138～6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.

Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.
Humans ; Heart Failure/metabolism* ; Myocardium/metabolism* ; Ketone Bodies/metabolism* ; Cardiovascular Diseases ; Fatty Acids/metabolism* ; Energy Metabolism

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Objective:To study the effects of salivary microbiota in patients with periodontitis on the tryptophan-aryl hydrocarbon receptor (AhR) signaling axis in mice with periodontitis and to provide theoretical basis as well as new ideas for the influences of periodontitis on systemic metabolism.Methods:Salivary microbiota of 12 healthy individuals and 14 patients with periodontitis were collected in Nanjing Stomatological Hospital, Medical School of Nanjing University from June to December of 2020. According to the random number table method, twenty-four mice were randomly divided into three groups: Sham group (control group), P group (periodontitis patients′ salivary microbiota group) and H group (periodontal healthy individuals′ salivary microbiota group). The maxillary second molars of all mice were treated with silk thread ligation to induce periodontitis. Phosphate buffer as well as salivary microbiota of periodontal healthy individuals and periodontitis patients were gavaged into periodontitis mice for 2 weeks. The expression of inflammatory factors in mice serum were detected by enzyme linked immunosorbent assay, and the expression of tryptophan and indole metabolites in intestinal tract and serum were detected by liquid chromatography-mass spectrometry. The expression of AhR in intestinal tract of mice was detected by immunohistochemistry and quantitative real time-PCR while gut microbiota constitution was detected by 16S rRNA gene sequencing. The remaining saliva samples of periodontitis patients and periodontal healthy individuals were applied to detect the expression of tryptophan and indole metabolites themselves.Results:The salivary microbiota of periodontitis patients could induce the expression of interleukin-1β [P group: (162.38±39.46) pg/ml, H group: (82.83±20.01) pg/ml; t=4.40, P=0.001) and tumor necrosis factor-α [P group: (361.16±123.90) pg/ml, H group: (191.66±106.87) pg/ml; t=2.54, P=0.030) in serum of periodontitis mice, and reduce the expression of AhR in colon (P group: 1.18±0.05, H group:1.83±0.47; t=3.09, P=0.015) and ileum (P group: 0.80±0.13, H group: 1.18±0.11; t=4.93, P=0.001). After gavage of salivary microbiota of periodontitis patients to the mice, tryptophan (P group: (18.1±3.8)×10 7, H group: (26.6±6.6)×10 7; t=2.49, P=0.037] and indole lactic acid [P group: (1.9±0.7)×10 7, H group: (3.7±0.6)×10 7; t=4.49, P=0.002) in serum of periodontitis mice were significantly decreased, but was relatively disorder in intestinal tract. However, the expressions of tryptophan and indole metabolites in saliva of periodontitis patients were higher than those of periodontal healthy individuals. There were significant differences in indole propionic acid [P group: (1 239.39±818.72) nmol/L, H group: (56.96±38.33) nmol/L; t=2.83, P=0.022]. What we find noteworthy was that the expressions of indolelactic acid metabolism in saliva, serum and intestinal were consistent, and salivary microbiota of periodontitis patients could reduce the relative abundance of indolelactic acid-producing bacteria in the gut, suggesting that the salivary microbiota of periodontitis patients might affect the expression of AhR through gut microbiota disorder and indolelactic acid downregulation. Conclusions:Salivary microbiota in patients with periodontitis may affect the systemic inflammatory state through down-regulating the expression of tryptophan-AhR signal axis.

Objective:To investigate the consistency and diagnostic efficiency of Chinese Thyroid Imaging Reporting and Date System (C-TIRADS) in thyroid nodule evaluation by different seniority sonographers.Methods:The preoperative ultrasonographic datum of 134 thyroid nodules in 112 patients from January to November 2020 were independently analyzed by sonographers with different seniority. According to the C-TIRADS guidelines, the C-TIRADS ultrasonographic indicators of each nodule were recorded and C-TIRADS classification was performed. Cohen′s Kappa (K) statistical method was used to analyze the consistency of ultrasonic indicators evaluated by different seniority sonographers. Using postoperative pathological results as the gold standard, the diagnostic efficacy of C-TIRADS classification for differentiating benign and malignant thyroid nodules by junior and senior sonographers was calculated respectively, and the Receiver Operating Characteristic (ROC) curves were drawn respectively.Results:The solid structure and vertical orientation of thyroid nodule judged by different seniority sonographers were very consistent ( K=0.84, 0.81). The consistencies of very hypoechoic and microcalcifications were substantial agreement ( K=0.80, 0.61), and moderate ( K=0.531) for the margin of the nodules. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of distinguishing benign and malignant thyroid nodules by junior and senior sonographers were 91.8%, 65.8%, 77.6%, 69.1%, 90.6% and 96.7%, 67.1%, 80.6%, 71.1%, 96.1%, respectively. The corresponding area under the ROC curves were 0.788 and 0.819, respectively ( Z=1.369, P=0.171). Conclusion:Ultrasonologists with different experience have good consistency in evaluating the C-TIRADS ultrasonic indicators of thyroid nodule, and the diagnostic efficacy of C-TIRADS classification in differentiating benign and malignant thyroid nodule was similar.