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*

Objective To investigate the distribution of pathogens and changes in serum humanβ-defendin-3(HBD3)and FMS like tyrosine kinase 3 ligand(Flt3L)levels in patients with pulmonary infection after esophageal cancer radical surgery.Methods Prospectively,patients who underwent radical resection of esophageal cancer and developed pulmonary infection from January 2022 to January 2024 were selected as the infection group(75 cases),and patients who underwent radical resection of esophageal cancer and did not develop pulmonary infection were selected as the non-infection group(93 cases).Patients in the infection group were divided into the mild group(25 cases),the moderate group(39 cases),and the severe group(11 cases)based on the CURB-65 score.The distribution of pathogenic bacteria in patients of the infection group was analyzed by the fully automatic microbial identification instrument.The expression levels of HBD3 and Flt3L in serum were detected by enzyme-linked immunosorbent assay(ELISA).Multivariate Logistic regression was applied to analyze the risk factors for postoperative pulmonary infection in esophageal cancer patients.ROC curve was applied to analyze the diagnostic value of HBD3 and Flt3L levels for postoperative pulmonary infection in esophageal cancer patients.Results Among 75 infected patients,90 strains of pathogens were detected,including 49 strains(54.44％)of Gram negative bacteria,29 strains(32.22％)of Gram positive bacteria,and 12 strains(13.33％)of fungi.The serum HBD3 and Flt3L levels in the infection group were greatly higher than those in the non infection group(P＜0.05).The serum HBD3 and Flt3L levels in the severe group were higher than those in the moderate group and mild group(P＜0.05),while the serum HBD3 and Flt3L levels in the moderate group were higher than those in the mild group(P＜0.05).Multivariate Logistic regression analysis showed that HBD3,Flt3 L,tumor location in the upper/middle segment,intraoperative bleeding ≥ 500 ml,diabetes,and smoking history were all factors influencing the pulmonary infection after radical resection of esophageal cancer(P＜0.05).According to the ROC curve,the AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum HBD3 level alone was 0.789.The AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum Flt3L level alone was 0.863,the AUC value of the combined diagnosis of the two was 0.934,which was greatly higher than that of the individual diagnosis(Zcombination vs HBD3=3.723,Zcombination vs Flt3L=2.098,P＜0.05).Conclusion The serum HBD3 and Flt3L levels in patients with pulmonary infection after esophageal cancer radical surgery are highly expressed,and the serum HBD3 and Flt3L levels are correlated with the severity of pulmonary infection.The two are risk factors for postoperative pulmonary infection in esophageal cancer patients after radical surgery,and their combination can effectively diagnose postoperative pulmonary infection in esophageal cancer patients.

Objective To investigate the distribution of pathogens and changes in serum humanβ-defendin-3(HBD3)and FMS like tyrosine kinase 3 ligand(Flt3L)levels in patients with pulmonary infection after esophageal cancer radical surgery.Methods Prospectively,patients who underwent radical resection of esophageal cancer and developed pulmonary infection from January 2022 to January 2024 were selected as the infection group(75 cases),and patients who underwent radical resection of esophageal cancer and did not develop pulmonary infection were selected as the non-infection group(93 cases).Patients in the infection group were divided into the mild group(25 cases),the moderate group(39 cases),and the severe group(11 cases)based on the CURB-65 score.The distribution of pathogenic bacteria in patients of the infection group was analyzed by the fully automatic microbial identification instrument.The expression levels of HBD3 and Flt3L in serum were detected by enzyme-linked immunosorbent assay(ELISA).Multivariate Logistic regression was applied to analyze the risk factors for postoperative pulmonary infection in esophageal cancer patients.ROC curve was applied to analyze the diagnostic value of HBD3 and Flt3L levels for postoperative pulmonary infection in esophageal cancer patients.Results Among 75 infected patients,90 strains of pathogens were detected,including 49 strains(54.44％)of Gram negative bacteria,29 strains(32.22％)of Gram positive bacteria,and 12 strains(13.33％)of fungi.The serum HBD3 and Flt3L levels in the infection group were greatly higher than those in the non infection group(P＜0.05).The serum HBD3 and Flt3L levels in the severe group were higher than those in the moderate group and mild group(P＜0.05),while the serum HBD3 and Flt3L levels in the moderate group were higher than those in the mild group(P＜0.05).Multivariate Logistic regression analysis showed that HBD3,Flt3 L,tumor location in the upper/middle segment,intraoperative bleeding ≥ 500 ml,diabetes,and smoking history were all factors influencing the pulmonary infection after radical resection of esophageal cancer(P＜0.05).According to the ROC curve,the AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum HBD3 level alone was 0.789.The AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum Flt3L level alone was 0.863,the AUC value of the combined diagnosis of the two was 0.934,which was greatly higher than that of the individual diagnosis(Zcombination vs HBD3=3.723,Zcombination vs Flt3L=2.098,P＜0.05).Conclusion The serum HBD3 and Flt3L levels in patients with pulmonary infection after esophageal cancer radical surgery are highly expressed,and the serum HBD3 and Flt3L levels are correlated with the severity of pulmonary infection.The two are risk factors for postoperative pulmonary infection in esophageal cancer patients after radical surgery,and their combination can effectively diagnose postoperative pulmonary infection in esophageal cancer patients.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4％(191/1 037),20.5％(185/902),and 22.4％(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8％to 89.6％.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.

Pancreatic polypeptide(PP),a pancreatic hormone containing 36 amino acids,plays impor-tant roles in the diagnosis and evaluation of pancreatic function,injury and diseases.In this study,a phage nanobody library against PP was constructed to screen specific PP nanobodies,which would be used to evaluate whether they have binding activity with PP antigen.After PP antigen with high purity was prepared by prokaryotic expression system,it was used to immunize alpaca to construct the nanobody li-brary against PP with high storage capacity and high abundance,from which 8 strains of PP nanobodies were obtained by phage display.One of nanobody strain(PP-VHH)was selected to be expressed in a prokaryotic expression system,which was induced overnight by IPTG.After purification and identifica-tion,the antigen-antibody binding activity and PP level in serum were detected by indirect ELISA and Sandwich ELISA methods,respectively.The results showed that PP-VHH had binding activity with PP,which could be used to detect PP in chicken and human serum.The Sandwich ELISA methods with R2 of the fitting curve 0.9868 could be used to detect PP concentrations of 48-55 pg/mL in the serum of chick-ens,while the concentrations of PP in human serum varied significantly.In summary,PP-VHH screened from nanobody library against PP could detect PP in serum,which would supply the basis for evaluation of abnormal pancreatic function and diagnosis of relative disease.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*