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*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

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*

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Objective:To summarize and discuss the clinical effect of different forms of anterolateral femoral perforator flap in the repair of acute lower extremity lesions based on the theory of damage control orthopaedics (DCO).Methods:The clinical data of 33 patients with acute destructive wounds in the lower limbs admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to December 2022 were retrospectively analyzed. Under the guidance of the DCO theory, the combined injuries were treated through multidisciplinary consultation, and at the same time, first-stage debridement, bone stent restoration, limb blood transport reconstruction, nerve tendon repair and temporary vacuum sealing drainage (VSD) dressing were applied. After the systemic condition was stabilized, the wound was repaired with anterolateral femoral perforator flaps of different forms. The defect area was 8.0 cm×5.0 cm-35.0 cm×25.0 cm, and the donor flap area was closed in one stage in all cases.Results:30 cases of skin flap survived completely after operation, 2 cases had distal partial necrosis, wound healing after dressing change, 1 case had delayed complete necrosis. The follow-up time was 9-25(14.7±5.3)months. 2 patients were treated with the second stage of repair surgery due to the bloated flap. The rest were satisfied with the shape of the reconstructed flap and the donor flap area, and the ankle joint function score was good.Conclusions:DCO theory combined with anterolateral femoral perforator flap is a safe and effective way to repair the mutilated wounds of lower limbs.

Objective:To investigate the incidence, clinical characteristics, and impact of spontaneous portosystemic shunt (SPSS) in patients with liver cirrhosis combined with hepatic encephalopathy (HE).Methods:The basic clinical and follow-up data were retrospectively analyzed for patients diagnosed with cirrhosis combined with HE at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2017 to December 2022. The patients were divided into large and small SPSS groups and a control group based on the results of abdominal enhanced CT or MRI.The clinical characteristics and outcome differences were compared among the three groups. Kaplan-Meier survival curves were used to compare HE-free survival time and overall survival time among the three groups. The log-rank test was used to compare the differences between groups. Cox regression analysis was used to identify the relevant risk factors affecting HE-free survival time and overall survival time.Results:A total of 223 cases with liver cirrhosis combined with HE were enrolled, including 150 in the SPSS and 73 in the control groups. The incidence rate of SPSS was 67.3% (150/223). The group was divided into small SPSS (79/150, 52.7%) and large SPSS group (71/150, 47.3%) according to the cross-sectional area of the diversion channel. The HE-free survival was shorter in the small and large SPSS groups compared with the control group (35.5 months in the small SPSS group and 21.3 months in the large SPSS group; P<0.001). The HE-free survival time was shorter in the large SPSS than with small SPSS group ( P=0.003). The overall survival time in the small SPSS group and the large SPSS group was shorter compared with the control group (small SPSS group: 39.4 months, large SPSS group: 52.9 months; P<0.001). There was no statistically significant difference in overall survival time between the small SPSS and large SPSS groups ( P=0.700). Cox regression analysis showed that SPSS was an independent risk factor affecting patients' HE-free survival time and overall survival time ( P<0.05). Conclusion:SPSS is more common in patients with liver cirrhosis combined with HE. Patients who combined with SPSS showed significant reductions in both HE-free survival time and overall survival time, especially evident in those with combined large SPSS.

Objective:To summarize and discuss the clinical effect of different forms of anterolateral femoral perforator flap in the repair of acute lower extremity lesions based on the theory of damage control orthopaedics (DCO).Methods:The clinical data of 33 patients with acute destructive wounds in the lower limbs admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to December 2022 were retrospectively analyzed. Under the guidance of the DCO theory, the combined injuries were treated through multidisciplinary consultation, and at the same time, first-stage debridement, bone stent restoration, limb blood transport reconstruction, nerve tendon repair and temporary vacuum sealing drainage (VSD) dressing were applied. After the systemic condition was stabilized, the wound was repaired with anterolateral femoral perforator flaps of different forms. The defect area was 8.0 cm×5.0 cm-35.0 cm×25.0 cm, and the donor flap area was closed in one stage in all cases.Results:30 cases of skin flap survived completely after operation, 2 cases had distal partial necrosis, wound healing after dressing change, 1 case had delayed complete necrosis. The follow-up time was 9-25(14.7±5.3)months. 2 patients were treated with the second stage of repair surgery due to the bloated flap. The rest were satisfied with the shape of the reconstructed flap and the donor flap area, and the ankle joint function score was good.Conclusions:DCO theory combined with anterolateral femoral perforator flap is a safe and effective way to repair the mutilated wounds of lower limbs.

Objective:To investigate the incidence, clinical characteristics, and impact of spontaneous portosystemic shunt (SPSS) in patients with liver cirrhosis combined with hepatic encephalopathy (HE).Methods:The basic clinical and follow-up data were retrospectively analyzed for patients diagnosed with cirrhosis combined with HE at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2017 to December 2022. The patients were divided into large and small SPSS groups and a control group based on the results of abdominal enhanced CT or MRI.The clinical characteristics and outcome differences were compared among the three groups. Kaplan-Meier survival curves were used to compare HE-free survival time and overall survival time among the three groups. The log-rank test was used to compare the differences between groups. Cox regression analysis was used to identify the relevant risk factors affecting HE-free survival time and overall survival time.Results:A total of 223 cases with liver cirrhosis combined with HE were enrolled, including 150 in the SPSS and 73 in the control groups. The incidence rate of SPSS was 67.3% (150/223). The group was divided into small SPSS (79/150, 52.7%) and large SPSS group (71/150, 47.3%) according to the cross-sectional area of the diversion channel. The HE-free survival was shorter in the small and large SPSS groups compared with the control group (35.5 months in the small SPSS group and 21.3 months in the large SPSS group; P<0.001). The HE-free survival time was shorter in the large SPSS than with small SPSS group ( P=0.003). The overall survival time in the small SPSS group and the large SPSS group was shorter compared with the control group (small SPSS group: 39.4 months, large SPSS group: 52.9 months; P<0.001). There was no statistically significant difference in overall survival time between the small SPSS and large SPSS groups ( P=0.700). Cox regression analysis showed that SPSS was an independent risk factor affecting patients' HE-free survival time and overall survival time ( P<0.05). Conclusion:SPSS is more common in patients with liver cirrhosis combined with HE. Patients who combined with SPSS showed significant reductions in both HE-free survival time and overall survival time, especially evident in those with combined large SPSS.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Superior vena cava syndrome(SVCS)is a group of clinical syndromes caused by obstruction of the superior vena cava and its major branches from various causes.Pulmonary artery stenosis(PS)is a complication of lung cancer or mediastinal tumours.SVCS combined with PS due to pulmonary metastases from bladder cancer is extremely rare and has not been reported in the literature.Here we reported an old male patient with pulmonary metastases from bladder cancer presenting with swelling of the head,neck and both upper limbs.SVCS combined with PS was clarified by pulmonary artery computed tomography angiography(CTA)and digital subtraction angiography(DSA).Endovascular stenting was used to treat SVCS.Angiography also showed that PS had not caused pulmonary hypertension and did not need to be treated.The swelling of the patient's head,neck and upper limbs was gradually reduced after the procedure.