Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China

OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

italic>Polygonum capitatum is a characteristic Miao medicine in Guizhou, commonly used in clinical practice to treat gastrointestinal and urinary tract infections. Research has found that it has good antibacterial and anti-inflammatory effects, and its main active ingredient is flavonoids. Lavonoid O-methyltransferase (FOMT) is a key enzyme for oxymethylation modification of flavonoid compounds. In order to understand the function and properties of FOMT protein in Polygonum capitatum, the transcriptome was sequenced by Illumina HiSeq 4000 high throughput sequencing technology. Then, the obtained transcripts were annotated and analyzed, and the whole genome of the FOMT gene family in Polygon capitalis was mined and identified. A total of 99 298 Unigenes were obtained, of which 71 514 were successfully annotated by the public database. In the genome of Polygonum capitatum, a total of 50 FOMT genes were identified. The phylogenetic tree showed that FOMT genes were divided into two subfamilies: caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT). Gene sequence analysis showed that the number of FOMT encoded amino acids ranged from 99 to 1 053 aa, the molecular weight ranged from 11 224.91 to 86 687.42 Da, and the isoelectric point ranged from 4.79 to 9.45. The 50 FOMT family members were hydrophobic proteins. Subcellular localization results showed that 54% of FOMT subfamily CCoAOMT and COMT members were located in cytoplasm and 28% were located in chloroplasts. The FOMT gene was tissue specific and highly expressed in the flowers of Polygonum capitatum, followed by the stems, and the least expressed in the roots. In this study, the FOMT gene family of Polygonum capitatum was identified and analyzed to provide theoretical basis for further study of FOMT function and biosynthesis of methylated flavonoids.

Aim To construct a DC-targeted modified(lacto-N-fucop-entose Ⅲ,LewisX)Pseudomonas aeruginosa(PA)DNA vaccine PLGA nanoparticle(LewisX-PLGA)loading PA PcrV and OprF genes combination,and provide a new idea for the prevention of PA clinical infection.Methods The PLGA nano-particles loading PA PcrV and OprF combined DNA(PLGA+PcrV/OprF)or loading pEGFP(PLGA+pEGFP)were pre-pared by double emulsification-solvent evaporation method.On this basis,the DC-SIGN-targeted ligand LewisX was connected to the surface of PLGA nanoparticles by amide condensation reac-tion.LewisX-modified PLGA-PcrV/OprF(LewisX-PLGA+PcrV/OprF)and LewisX-modified PLGA-pEGFP(LewisX-PL-GA+pEGFP)were prepared.Particle size,Zeta potential,en-capsulation rate and drug loading were evaluated to characterize LewisX-PLGA+PcrV/OprF.The cytotoxicity of LewisX-PLGA+PcrV/OprF was investigated by CCK-8.DC targeting of LewisX-PLGA+pEGFP was validated in vitro transfection.Further,LewisX-PLGA+PcrV/OprF lysosome escape was used to evalu-ate the targeting performance of LewisX-modified PLGA nanopar-ticles loading DNA in vitro.The immunoefficacy of the nanopar-ticles was evaluated by detecting the level of lymphocyte prolifer-ation,humoral immunity and immune protection.Results The diameter of LewisX-PLGA+PcrV/OprF was(201.17±1.6)nm.The encapsulation efficiency of LewisX-PLGA+PcrV/OprF was(85.72±5.3)％.The Zeta potential of LewisX-PLGA+PcrV/OprF was+(31.17±1.8)mV.In the DC2.4 cytotoxici-ty test,the cell survival rates were above 85％.The results of fluorescence microscopy after LewisX-PLGA+pEGFP transfec-tion in vitro showed that LewisX-PLGA+pEGFP was more readi-ly taken up by DC2.4,and LewisX-PLGA+pEGFP had a DC-SIGN specific targeting performance.The CLSM's observation of LewisX-PLGA+Pcrv/OprF showed that more DNA escaped from the lysosome into the cytoplasm.The results suggested that LewisX-PLGA had DC2.4 targeting performance.Because DC2.4 cells endocyted more LewisX-PLGA+Pcrv/OprF into the lysosome,the amount of DNA carried by the nanoparticles esca-ping into the cytoplasm increased.in vivo immune results showed that the lymphocyte proliferation level and antibody titer level of targeted DNA vaccine increased significantly,further improved the survival rate of mice infected with acute pneumoni-a,and reduced the bacterial load of mouse lungs.Conclusions The DC-SIGN-targeted aptamer-modified PA DNA vaccine nanoparticle LewisX-PLGA can be successfully constructed.It promotes the transfection of DNA into DC.It promotes the endo-cytosis of PA DNA vaccine into the DC lysosome and the escape of PA DNA into the cytoplasm.This results in a significant im-mune response in body,which enhances the protective efficacy of vaccine.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

OBJECTIVES: To investigate the value of CCKBR^fl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). METHODS: In the first part, 2-month-old CCKBR^fl/fl villin-Cre mice (CKO) and control CCKBR^fl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS: The CCKBR^fl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBR^fl/fl villin-Cre mice, but no significant histopathological changes were observed. CONCLUSIONS These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBR^fl/fl villin-Cre mice. The CCKBR^fl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

Humans ; Gemcitabine ; Neoplasms

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.
Humans ; Retrospective Studies ; Atrial Fibrillation ; Heart Septum/surgery* ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery*