This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

Objective To investigate the application value of spectral CT multi-quantitative parameters combined with clinical characteristics in predicting high-risk gastroesophageal varices(GOV)in patients with liver cirrhosis.Methods The results of upper abdominal spectral CT enhancement and electronic gastroscopy in 112 patients diagnosed with liver cirrhosis were analyzed retrospec-tively,and the clinical data were collected.According to the gastroscopic manifestations,the patients were divided into high-risk GOV group(n=74)and low-risk GOV group(n=38).Univariate analysis was used to compare the spectral CT quantitative parameters and clinical characteristics between the two groups.Multivariate logistic regression analysis was used to screen the independent risk factors for high-risk GOV.R software was used to construct a nomogram model for predicting high-risk GOV,and the differentia-tion,calibration and clinical practicability of the prediction model were evaluated.Results The normalized iodine concentration(NIC)of liver left lobe,prothrombin time(PT),albumin(ALB)and liver function grading were independent risk factors for high-risk GOV(P＜0.05).The area under the curve(AUC)of receiver operating characteristic(ROC)curve of predicting high-risk GOV in nomo-gram model was 0.893.Calibration curve showed that the predicted results were basically consistent with the actual results.Decision curve analysis(DCA)showed that the prediction model had good clinical practicability.Conclusion The nomogram model based on NIC of liver left lobe,PT,ALB and liver function grading is helpful to predict patients with high-risk GOV in liver cirrhosis,and pro-vides a reference for clinical prevention and treatment of esophagogastric variceal bleeding(EVB).

Objective To investigate the application value of spectral CT multi-quantitative parameters combined with clinical characteristics in predicting high-risk gastroesophageal varices(GOV)in patients with liver cirrhosis.Methods The results of upper abdominal spectral CT enhancement and electronic gastroscopy in 112 patients diagnosed with liver cirrhosis were analyzed retrospec-tively,and the clinical data were collected.According to the gastroscopic manifestations,the patients were divided into high-risk GOV group(n=74)and low-risk GOV group(n=38).Univariate analysis was used to compare the spectral CT quantitative parameters and clinical characteristics between the two groups.Multivariate logistic regression analysis was used to screen the independent risk factors for high-risk GOV.R software was used to construct a nomogram model for predicting high-risk GOV,and the differentia-tion,calibration and clinical practicability of the prediction model were evaluated.Results The normalized iodine concentration(NIC)of liver left lobe,prothrombin time(PT),albumin(ALB)and liver function grading were independent risk factors for high-risk GOV(P＜0.05).The area under the curve(AUC)of receiver operating characteristic(ROC)curve of predicting high-risk GOV in nomo-gram model was 0.893.Calibration curve showed that the predicted results were basically consistent with the actual results.Decision curve analysis(DCA)showed that the prediction model had good clinical practicability.Conclusion The nomogram model based on NIC of liver left lobe,PT,ALB and liver function grading is helpful to predict patients with high-risk GOV in liver cirrhosis,and pro-vides a reference for clinical prevention and treatment of esophagogastric variceal bleeding(EVB).

Objective:To explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Objective:To explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Objective:Molecular mechanisms underlying compound heterozygous mutations in a patient with inherited antithrombin (AT) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018 with a one-day history of sudden syncope and limb twitching. Peripheral venous blood was collected from the proband and members of his lineages, totaling nine persons across three generations, and a family lineage survey was conducted. AT activity (AT:A) was measured using a chromogenic substrate assay, while AT antigen (AT:Ag) was detected through an immunoturbidimetric assay. Mutation sites were identified by means of Sanger sequencing of the SERPINC1 gene, and silico tools were applied to predict the mutational conservation and hydrophobicity changes. Recombinant plasmid expression vectors were constructed and transfected into HEK293T cells for in vitro overexpression studies. The recombinant AT protein was characterized using Western Blotting, ELISA, and cellular immunofluorescence assays.Results:The proband was a 21-year-old man with type Ⅰ AT deficiency. His AT:A was 33%, along with a corresponding reduction in AT:Ag. The genetic analysis revealed there was a heterozygous insertion mutation at c.318_319insT (p.Asn107*) and a heterozygous missense mutation at c.922G>T (p.Gly308Cys) in exons 2 and 5, respectively. These mutation sites were entirely conserved among the homologous species. Additionally, hydrophobicity studies showed that the p.Gly308Cys mutation will decrease the hydrophilicity of amino acid residues 307-313. The in vitro expression studies indicated a reduction of approximately 46.98%±2.94% and 41.35%±1.48% in the amount of recombinant protein AT-G308C in transfected cell lysates and culture supernatants, respectively. Treatment with the proteasome inhibitor (MG132) restored the cytoplasmic levels of AT-G308C protein to a level similar to that of wild-type protein. However, neither cell lysate nor culture supernatant demonstrated the presence of the recombinant protein AT-N107*. Conclusions:The heterozygous insertion mutation of p.Asn107* and the heterozygous missense mutation of p.Gly308Cys have been associated with reduced AT levels in proband. The p.Asn107* heterozygous insertion mutation may initiate the degradation of mRNA via nonsense mutation-mediated mechanisms, which would remove the defective transcripts, as well as the p.The Gly308Cys heterozygous missense mutation may cause the AT protein to undergo proteasome-dependent degradation by modifying the hydrophobicity of nearby residues in the cytoplasm.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.