OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
Animals ; Alzheimer Disease/pathology* ; Pseudogenes/genetics* ; Mice ; Memory Disorders/metabolism* ; MicroRNAs/genetics* ; Disease Models, Animal ; Spatial Learning/physiology* ; Mice, Transgenic ; Presenilin-1/genetics* ; Male ; Amyloid Precursor Protein Secretases/metabolism* ; Mice, Inbred C57BL ; Aspartic Acid Endopeptidases/metabolism*

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Objective To explore the characteristics of oropharyngeal metabolites of postoperative pneumonia(POP)and non-POP patients with gastric cancer by non-targeted metabolomics,and to provide reference for revea-ling the pathogenesis as well as clinical prevention and control.Methods Oropharyngeal swabs were collected from patients who underwent surgical treatment for gastric cancer in the department of gastrointestinal surgery of a tertia-ry hospital in Fujian Province from January 2022 to December 2023,nested case-control study was adopted,with 30 cases in POP group and non-POP group,respectively,ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)technique was adopted for detection,and multivariate statistical analysis was per-formed.Results The metabolites of POP group and non-POP group preoperatively,POP group and non-POP group postoperatively,POP group preoperatively and postoperatively,as well as non-POP group preoperatively and post-operatively did not show a clear trend of separation on the score graph of principal component analysis(PCA),par-tial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA),but the screening of the differential metabolites revealed that the relative abundances of ascorbic acid and lipoic acid in the POP group preoperatively were lower than non-POP group preoperatively.The relative abundance of 5'-adenylic acid in the POP group preoperatively was lower than postoperatively,while the relative abundances of suc-cinic acid and phenylacetaldehyde were higher.There were differences in metabolic pathways such as phenylalanine.Conclusion Alteration of metabolite level due to abnormalities in specific metabolic pathways presents in the deve-lopment of gastric cancer POP and may be related to the development of POP.

Objective To analyze the situation of blood lipid and blood routine parameters in patients with pneumoconiosis,and construct a column chart diagnostic model to explore their diagnostic value for pneumo-coniosis.Methods A total of 456 patients with pneumoconiosis admitted to the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College from January 2022 to January 2024 were selected as the pneu-moconiosis group,while 462 healthy subjects exposed to dust during the same period were chosen as the con-trol group.Serum lipids and blood routine parameters related to pneumoconiosis were measured and compared between two groups.Univariate and multivariate Logistic regression analyzes were conducted to examine ser-um lipids and blood routine parameters associated with pneumoconiosis.A risk prediction model was construc-ted using logistic regression in machine learning,and the diagnostic efficacy of the column chart diagnostic model was evaluated by calculating the C-index through receiver operating characteristic(ROC)curve and plotting the model calibration curve based on Hosmer Lemeshow goodness of fit.Decision curve analysis(DCA)was used to assess the clinical practicality of the column chart diagnostic model.Results The levels of serum high-density ester protein cholesterol(HDL-C),cholesterol(TC),red blood cell(RBC),hematocrit(HCT),hemoglobin concentration(HGB),lymphocyte number(LYM),and lymphocyte percentage(LYM％)in the pneumoconiosis group were lower than those in the control group(P＜0.05).The levels of neutrophil-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune inflammation index(SII)were higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that HDL-C,LYM％,PLR,and SII were independent influencing factors for pneumoconiosis(P＜0.05).A column chart diagnostic model for the occurrence of pneumoconiosis was constructed using HDL-C,TC,LYM％,PLR,and SII as diagnostic factors.The ROC curve C-index of the diagnostic model was 0.84(95％CI:0.81-0.86),with sensitivity for diagnosing pneumoconiosis of 75.29％,specificity of 77.51％,posi-tive predictive value of 83.25％,and negative predictive value of 67.88％.Internal validation was conducted on the constructed column chart diagnostic model,with a validation set ROC curve C-index of 0.84(95％CI:0.80-0.87),sensitivity of 80.91％,specificity of 72.62％,positive diagnostic value of 79.46％,and negative diagnostic value of 74.39％.The calibration positive curve slope of the diagnostic model was close to 1,and in the fit test P＞0.05.DCA analysis showed that the diagnostic model had clinical practical value for risk diag-nosis of pneumoconiosis.Conclusion HDL-C,TC,LYM％,PLR and SII are independent influencing factors for pneumoconiosis.A column chart diagnostic model for the occurrence of pneumoconiosis is successfully constructed based on machine learning principles,and it has been verified to have high diagnostic efficiency.

Objective:To evaluate the short-term efficacy of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early-stage gastric cancer.Methods:This is a retrospective case series study. Data of 17 consecutive early gastric cancer patients from a prospective cohort at Beijing Friendship Hospital,Capital Medical University were analyzed between August 2023 and August 2024. Sixteen cases were from the department of general surgery and 1 from the department of gastroenterology. The cohort included 9 males and 8 females,with a mean age of 61.4 years (range: 46 to 79 years). Clinical data,including demographics,pathological features,surgical procedures,and follow-up outcomes,were collected through medical records and databases. All patients were followed for over 3 months,with follow-up ending on December 5,2024.Results:A total of 17 patients were involved. Among them, 5 patients underwent endoscopic submucosal dissection (ESD) combined with laparoscopic sentinel lymph node dissection (LSBD),and another 3 patients who underwent complete ESD resection received LSBD due to pathological stage meeting the expanded indications. 6 patients who underwent non-curative ESD resection received laparoscopic gastric regional resection (LRG) combined with LSBD,and another 3 patients directly received LRG combined with LSBD. The average number of sentinel lymph nodes dissected before surgery ( M(IQR)) was 8.9 (4.5) (range: 4 to 21),and the detection rate and accuracy rate were both 100%. Postoperative pathology confirmed that there was no metastasis in the sentinel lymph nodes of 5 patients who underwent ESD combined with LSBD and 3 patients who underwent LSBD after complete ESD resection. The vertical and horizontal margins of ESD were all negative. One patient was an absolute indication for ESD. For the 6 patients who underwent non-curative ESD resection combined with LRG and LSBD,the horizontal margins were all negative. Two patients showed 1 metastasis in each of the 21 and 9 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed during the operation. Postoperatively,73 and 39 lymph nodes were retrieved respectively. The former had 1 additional metastasis,while the latter had no metastasis. Among the 3 patients who underwent direct LRG combined with LSBD,the horizontal margins were negative. One patient was confirmed as an absolute indication for ESD by postoperative pathology,and one patient had 1 metastasis in 8 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed. Postoperatively,there was no metastasis in 54 lymph nodes. All patients had no complications such as infection,bleeding,perforation,or death after surgery. Among the 14 patients who did not receive additional radical surgery,they were able to pass gas and defecate within 3 days after surgery,with an average hospital stay of 6 days. The nutritional indicators and gastric radionuclide emptying imaging half-emptying time were similar to those before surgery at 3 months after surgery. Conclusions:Laparoscopic and endoscopic cooperative regional gastrectomy with sentinel lymph node basin dissection has the advantages of minimal invasiveness,preservation of gastric function,and precise treatment. It maybe suitable for patients with early-stage gastric cancer at high risk of lymph node metastasis and has good short-term efficacy.