Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To investigate the contributing factors to elevated blood pressure in borderline cases during medical selection for recruitment of Air Force flying cadets in order to enhance the accuracy of selection.Methods:Blood pressure was measured among 2 350 male high school graduates in the 2022 re-selection phase of medical selection of Air Force flying cadets. None of the participants had a family history of hypertension according to previous health checkups. Identified through blood pressure measurement, subjects with borderline hypertension were assigned to an intervention group (self-intervention with personalized correction plans) and a control group (self-intervention alone) using a random number table. Standardized blood pressure measurements and comprehensive medical history reviews were performed to compare pre- and post-intervention outcomes across the 2 groups, followed by an investigation into the causative mechanisms of elevated blood pressure.Results:Among the 102 cases of borderline hypertension (51 per group) identified, primary contributing factors included the white-coat phenomenon (41.2%), pre-examination physical activity (17.6%), pre-examination medications (3.9%) and poor sleep quality (35.3%). No significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) were observed between the 2 groups at baseline (both P>0.05). After interventions, the intervention group showed significantly lower SBP ( t=3.13, P=0.002) and DBP ( t=7.68, P<0.001) than the control group. Both groups exhibited reductions in SBP and DBP from baseline ( t=6.63, 8.97, 4.13, 2.03, P<0.001, <0.001, <0.001, =0.043). The percentage of students with normal blood pressure was 96.1% (49/51) in the intervention group and 78.4% (40/51) in the control group. Conclusions:Transient blood pressure elevation in selection settings primarily stems from the white-coat phenomenon, physical exertion, medications and sleep disturbances. Standardizing blood pressure measurement protocols and addressing transient factors can help avoid unwarranted disqualifications and ensure the accuracy of selection.

Objective This study conducted a dynamic network analysis of the symptoms in patients with hepatocellular carcinoma(HCC)at different postoperative time points,aiming to explore evolving core symptoms and provide a basis for developing precise clinical symptom management programs.Methods A longitudinal study was carried out involving 370 HCC patients who underwent surgical treatment at a hospital in Kunming city between February and December 2024.Questionnaires were administered on postoperative day 2(T1)and day 7(T2),using the Chinese version of the Memory Symptom Assessment Scale.Symptom networks of 18 symptoms were constructed for both time points using R software to explore core symptoms and their interconnections.A network comparison test was also performed to assess differences between the 2 time points.Results All 370 patients completed the questionnaire at T1,and 357 valid responses were collected at T2,yielding a response rate of 96.49％.At T1,"feeling nervous"had the highest centrality(rs=1.29),while at T2,"feeling sad"was most central(rs=1.11).Overall strength of the symptom networks showed that notable changes were observed in the edge weights between symptoms(P=0.01).Conclusion While the overall structure of early postoperative symptoms in HCC patients remained relatively stable over time,the core symptoms shifted."Feeling nervous"emerged as the central symptom at T1,whereas"feeling sad"became predominant.Digestive-related symptoms are progressively more closely linked over time.Healthcare professionals should dynamically assess patients' early postoperative psychological symptoms and digestive system related symptoms,and focus on intervening with symptoms of tension and sadness.

Objective:To compare the efficacy of 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-octreotide (OC) PET/CT and MRI in detecting liver metastases (LM) of neuroendocrine neoplasm (NENLM). Methods:18F-AlF-NOTA-OC PET/CT and MRI findings (dynamic contrast enhanced MRI and diffusion weighted imaging) of 44 patients (26 males, 18 females, age (53.8±13.4) years) with neuroendocrine neoplasm (NEN) confirmed by pathological or clinical follow-up in the First Affiliated Hospital of Zhengzhou University from July 2021 to December 2023 were retrospectively analyzed. According to the size of LM, patients were divided into 3 groups with long diameter ≤1 cm, 1 cm< long diameter ≤2 cm and long diameter >2 cm. According to the 2019 WHO pathological grade, patients were divided into G1, G2, G3 and neuroendocrine carcinoma groups. McNemar χ2 test was used to compare the difference in detecting LM and lesions between the two methods. Results:The detection rate of 18F-AlF-NOTA-OC PET/CT and MRI in patients with NENLM was 95.45%(42/44). Among 44 patients, 227 lesions were detected by PET/CT and 303 were detected by MRI. Based on lesion analysis ( n=307), the detection rate of 18F-AlF-NOTA-OC PET/CT for NENLM was lower than that of MRI (73.94%(227/307) vs 98.70%(303/307); χ2=66.96, P<0.001). For NENLM with long diameter ≤1 cm, 1 cm < long diameter ≤2 cm, long diameter >2 cm, the detection rates of MRI were higher than those of 18F-AlF-NOTA-OC PET/CT (98.72%(77/78), 93.55%(116/124), 97.35%(110/113) vs 47.44%(37/78), 73.39%(91/124), 87.61%(99/113); χ2 values: 5.88-36.21, all P<0.05). Conclusions:Compared with 18F-AlF-NOTA-OC PET/CT, MRI has a higher detection rate for NENLM with different long diameters of NEN, especially for lesions with long diameter≤1 cm.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

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.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

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 evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

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