Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective:To quantitatively analyze right ventricular reverse remodeling in patients with severe tricuspid regurgitation after transcatheter tricuspid edge-to-edge repair (T-TEER) by two-dimensional speckle tracking echocardiography, and to preliminarily evaluate the clinical efficacy of this procedure.Methods:This study was a prospective single-center cohort study. Patients diagnosed with severe tricuspid regurgitation at the Xiamen Cardiovascular Hospital Xiamen University from March 2021 to June 2023 were enrolled. All patients underwent transthoracic echocardiography and transesophageal three-dimensional echocardiography before T-TEER, and transthoracic echocardiography at 30 days, 6 months, and 9 months after T-TEER. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including death, stroke, myocardial infarction, reoperation, arrhythmia, and conduction block. Other clinical evaluation indicators included New York Heart Association (NYHA) functional classification and tricuspid regurgitation grade.Results:A total of 34 patients were enrolled, aged (67.9±9.3) years, and 71% (24/34) were female. The median follow-up duration was 9 months. All patients achieved a reduction of tricuspid regurgitation by ≥2 grades at 9 months after T-TEER, with 79% (27/34) of them having mild to moderate tricuspid regurgitation. Transthoracic echocardiography at 9 months after T-TEER showed that the vena contracta width of tricuspid regurgitation ((5.42±2.33) mm vs. (11.54±4.05) mm, P<0.001), effective regurgitant orifice area ((0.24±0.09) cm2 vs. (0.52±0.14) cm2, P<0.001), regurgitant jet area ((7.95±4.02) cm2 vs. (13.93±6.10) cm2, P<0.001), inferior vena cava diameter ((19.38±2.63) mm vs. (23.56±3.31) mm, P<0.001), right ventricular end-diastolic diameter ((28.03±6.26) mm vs. (33.21±8.24) mm, P=0.001), and tricuspid annular diameter ((36.47±4.40) mm vs. (41.44±7.08) mm, P<0.001) were all reduced compared with baseline; while the tricuspid annular plane systolic excursion ((18.08±5.25) mm vs. (14.91±3.42) mm, P=0.005) and right ventricular fractional area change ((37.61±7.52)% vs. (30.79±9.06)%, P=0.004) were both increased compared with baseline. At 9 months after T-TEER, all patients had a NYHA functional classification of grade Ⅰ or Ⅱ, and no major adverse cardiovascular and cerebrovascular event occurred during the follow-up period. Conclusion:It is preliminarily confirmed that T-TEER is safe and effective in the treatment of severe tricuspid regurgitation, with significant right ventricular reverse remodeling observed in patients at 9 months after T-TEER.

Objective:To evaluate the clinical value of high-risk human papillomavirus (HPV) viral load for the cervical cancer screening and triage of high-risk HPV positive populations without additional tests.Methods:(1) This study conducted a retrospective analysis of 29 720 women aged 35-64 years who received cervical cancer screening in Quanzhou, China, in 2021. Fourteen high-risk HPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) were detected for cervical cancer primary screening using hybrid capture-chemiluminescence method. High-risk HPV positive samples were further subjected to HPV 16/18 genotyping using hybrid capture-chemiluminescence method. Among them, HPV 16/18 positive women were directly referred to colposcopy, while the other 12 high-risk HPV positive samples were further subjected to liquid based cytology test. Those with abnormal or suspicious cytology were referred to colposcopy. Biopsies were taken for histopathological examination of suspicious or abnormal individuals under colposcopy. (2) Ten cases of colposcopy loss or refusal to undergo examination were excluded, and the data from the 29 710 cases were analyzed. The HPV viral loads of the other 12 high-risk HPV positive populations were focused and evaluated their HPV viral loads for further cervical intraepithelial neoplasia (CIN) Ⅱ and above lesions (CINⅡ +) triage in cervical cancer screening. Results:(1) Among 29 720 women, 2 487 women (8.37%, 2 487/29 720) were positive for high-risk HPV, including 807 women (2.72%, 807/29 720) were positive for HPV 16/18 and 1 680 patients (5.65%, 1 680/29 720) were positive for the other 12 high-risk HPV types. Among 1 680 women who tested positive for the other 12 high-risk HPV types, 573 patients were atypical squamous cell carcinoma of unclear significance or above, 346 patients were CIN Ⅰ, 122 patients were CIN Ⅱ-Ⅲ, 9 patients were squamous cell carcinoma patients, and 4 patients were adenocarcinoma in situ. The immediate risk of CIN Ⅱ + in HPV 16/18 positive women (11.13%) was approximately four times higher than that of other 12 high-risk HPV positive women (2.74%). (2) Through the viral load analysis of the other 12 high-risk HPV types, we found that the viral load of the other 12 high-risk HPV provide a good value for the pathological results, with a clinical cutoff (CO) value of 11.21 relative light unit/CO (RLU/CO) for the CINⅡ + detection. Except for HPV 16/18 positive patients, when the viral load values of the other 12 high-risk HPV types were greater than 10 RLU/CO, these patients had a higher risk of CINⅡ +, with a positive predictive value of 31.29%. CINⅡ + was not found in any of the other 12 high-risk HPV positive with viral load values less than or equal to 10 RLU/CO. Conclusions:Using hybrid capture-chemiluminescence HPV tests for HPV 16/18 genotyping, combined with the viral loads (>10 RLU/CO) of the other 12 high-risk HPV analysis, one could triage HPV positive population without additional tests. Such triage strategy could promote the coverage of cervical cancer screening, particularly where cytology pathologists or economic resources are limited.

Objective:To evaluate the clinical value of high-risk human papillomavirus (HPV) viral load for the cervical cancer screening and triage of high-risk HPV positive populations without additional tests.Methods:(1) This study conducted a retrospective analysis of 29 720 women aged 35-64 years who received cervical cancer screening in Quanzhou, China, in 2021. Fourteen high-risk HPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) were detected for cervical cancer primary screening using hybrid capture-chemiluminescence method. High-risk HPV positive samples were further subjected to HPV 16/18 genotyping using hybrid capture-chemiluminescence method. Among them, HPV 16/18 positive women were directly referred to colposcopy, while the other 12 high-risk HPV positive samples were further subjected to liquid based cytology test. Those with abnormal or suspicious cytology were referred to colposcopy. Biopsies were taken for histopathological examination of suspicious or abnormal individuals under colposcopy. (2) Ten cases of colposcopy loss or refusal to undergo examination were excluded, and the data from the 29 710 cases were analyzed. The HPV viral loads of the other 12 high-risk HPV positive populations were focused and evaluated their HPV viral loads for further cervical intraepithelial neoplasia (CIN) Ⅱ and above lesions (CINⅡ +) triage in cervical cancer screening. Results:(1) Among 29 720 women, 2 487 women (8.37%, 2 487/29 720) were positive for high-risk HPV, including 807 women (2.72%, 807/29 720) were positive for HPV 16/18 and 1 680 patients (5.65%, 1 680/29 720) were positive for the other 12 high-risk HPV types. Among 1 680 women who tested positive for the other 12 high-risk HPV types, 573 patients were atypical squamous cell carcinoma of unclear significance or above, 346 patients were CIN Ⅰ, 122 patients were CIN Ⅱ-Ⅲ, 9 patients were squamous cell carcinoma patients, and 4 patients were adenocarcinoma in situ. The immediate risk of CIN Ⅱ + in HPV 16/18 positive women (11.13%) was approximately four times higher than that of other 12 high-risk HPV positive women (2.74%). (2) Through the viral load analysis of the other 12 high-risk HPV types, we found that the viral load of the other 12 high-risk HPV provide a good value for the pathological results, with a clinical cutoff (CO) value of 11.21 relative light unit/CO (RLU/CO) for the CINⅡ + detection. Except for HPV 16/18 positive patients, when the viral load values of the other 12 high-risk HPV types were greater than 10 RLU/CO, these patients had a higher risk of CINⅡ +, with a positive predictive value of 31.29%. CINⅡ + was not found in any of the other 12 high-risk HPV positive with viral load values less than or equal to 10 RLU/CO. Conclusions:Using hybrid capture-chemiluminescence HPV tests for HPV 16/18 genotyping, combined with the viral loads (>10 RLU/CO) of the other 12 high-risk HPV analysis, one could triage HPV positive population without additional tests. Such triage strategy could promote the coverage of cervical cancer screening, particularly where cytology pathologists or economic resources are limited.

Objective:To quantitatively analyze right ventricular reverse remodeling in patients with severe tricuspid regurgitation after transcatheter tricuspid edge-to-edge repair (T-TEER) by two-dimensional speckle tracking echocardiography, and to preliminarily evaluate the clinical efficacy of this procedure.Methods:This study was a prospective single-center cohort study. Patients diagnosed with severe tricuspid regurgitation at the Xiamen Cardiovascular Hospital Xiamen University from March 2021 to June 2023 were enrolled. All patients underwent transthoracic echocardiography and transesophageal three-dimensional echocardiography before T-TEER, and transthoracic echocardiography at 30 days, 6 months, and 9 months after T-TEER. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including death, stroke, myocardial infarction, reoperation, arrhythmia, and conduction block. Other clinical evaluation indicators included New York Heart Association (NYHA) functional classification and tricuspid regurgitation grade.Results:A total of 34 patients were enrolled, aged (67.9±9.3) years, and 71% (24/34) were female. The median follow-up duration was 9 months. All patients achieved a reduction of tricuspid regurgitation by ≥2 grades at 9 months after T-TEER, with 79% (27/34) of them having mild to moderate tricuspid regurgitation. Transthoracic echocardiography at 9 months after T-TEER showed that the vena contracta width of tricuspid regurgitation ((5.42±2.33) mm vs. (11.54±4.05) mm, P<0.001), effective regurgitant orifice area ((0.24±0.09) cm2 vs. (0.52±0.14) cm2, P<0.001), regurgitant jet area ((7.95±4.02) cm2 vs. (13.93±6.10) cm2, P<0.001), inferior vena cava diameter ((19.38±2.63) mm vs. (23.56±3.31) mm, P<0.001), right ventricular end-diastolic diameter ((28.03±6.26) mm vs. (33.21±8.24) mm, P=0.001), and tricuspid annular diameter ((36.47±4.40) mm vs. (41.44±7.08) mm, P<0.001) were all reduced compared with baseline; while the tricuspid annular plane systolic excursion ((18.08±5.25) mm vs. (14.91±3.42) mm, P=0.005) and right ventricular fractional area change ((37.61±7.52)% vs. (30.79±9.06)%, P=0.004) were both increased compared with baseline. At 9 months after T-TEER, all patients had a NYHA functional classification of grade Ⅰ or Ⅱ, and no major adverse cardiovascular and cerebrovascular event occurred during the follow-up period. Conclusion:It is preliminarily confirmed that T-TEER is safe and effective in the treatment of severe tricuspid regurgitation, with significant right ventricular reverse remodeling observed in patients at 9 months after T-TEER.

Objective:To quantitatively evaluate the left ventricular myocardial strains and global myocardial work indices in severe aortic stenosis(AS) patients with preserved left ventricular ejection fraction (LVEF) undergoing transcatheter aortic valve implantation (TAVI) by using two-dimensional speckle tracking imaging (2D-STI) technology and pressure-strain loop (PSL).Methods:Twenty patients undergoing TAVI from January to November 2020 in Cardiovascular Hospital of Xiamen University were selected as the TAVI group, and 20 healthy volunteers (with the matched gender, age) were selected as the control group at the same period. Left ventricular global longitudinal strain (GLS), endocardial, middle, epicardial myocardial longitudinal strain (LSendo, LSmid, LSepi) were measured by 2D-STI. The correlation between aortic pressure and the left ventricular systolic pressure invasively measured by cardiac catheterization, and blood pressure and the left ventricular systolic pressure non-invasively measured by peripheral brachial artery systolic blood pressure combined with Doppler-derived mean aortic gradient was separately compared. The non-invasive PSL was used to evaluate the global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). The differences of the myocardial strains and myocardial work indices between the two groups, including controls, patients with preoperation, 1 week and 3 months after TAVI, were compared.Results:Compared with the control group, GLS, LSendo, LSmid and LSepi of the left ventricle in the TAVI preoperation group were decreased (all P<0.05), LSendo increased at 1 week after TAVI, and GLS, LSendo, LSmid, and LSepi increased at 3 months after TAVI (all P<0.05). In the TAVI preoperative, invasive aortic pressure was positively correlated with peripheral brachial artery systolic blood pressure, invasive left ventricular systolic pressure was positively correlated with non-invasive left ventricular systolic pressure ( r=0.658, 0.565; all P<0.01). Compared with the control group, the preoperative the GWE decreased and the GWW increased in the TAVI group (all P<0.05). Compared with the preoperation, the GWI and GCW decreased at 1 week after TAVI (all P<0.05). Compared with 1 week after TAVI, GWI, GCW, GWE increased and GWW decreased at 3 months after TAVI (all P<0.05). Conclusions:The application of 2D-STI and PSL can quantitatively evaluate the left ventricular myocardial systolic function before and after TAVI in AS patients, which can provide a more objective reference index for clinical evaluation of the efficacy of TAVI.

We present a case report of a healthy neonate born by vaginal delivery to a woman who had recovered from COVID-19 after 37 days of discharge. The pregnant woman had fever, cough, and chills at 33 +1 gestational weeks and was diagnosed with COVID-19 by coronavirus nucleic acid test one day later. She recovered and was discharged after a series of treatment, and the 2019 novel coronavirus nucleic acid test and pulmonary CT were negative at the 2nd and 4th weeks after being discharged. The patient was admitted in early labor at 38 +4 gestational weeks and delivered a healthy newborn vaginally at that day. Both the mother and the baby were in good condition. All the maternal or neonatal specimens taken immediately after birth in the delivery room for 2019 novel coronavirus nucleic acid tests were negative, including the maternal pharynx, rectal and cervical secretions, amniotic fluid, an neonatal pharynx and rectal swabs. The qualitative examination of 2019 novel coronavirus antibodies in the maternal venous blood test showed that both IgG and IgM were positive. While the same test for neonatal cord blood and femoral vein blood showed negative results. No inflammatory reaction was found in the placenta and immunohistochemistry detection of novel coronavirus N protein was negative. The mother and newborn were observed postnatally and treated in the same ward, neither of them had fever, cough or fatigue, and were discharged three days after delivery. The qualitative examination of 2019 novel coronavirus antibodies (IgM and IgG) in the femoral vein blood of the nenonate 27 days old showed negative results.

Objective:To assess the changes of left ventricular systolic function and global synchronization and myocardial work in patients with left bundle branch pacing (LBBP) by two-dimensional multi-layered speckle tracking imaging.Methods:Forty-two patients with Ⅱ degree Ⅱ type or Ⅲ degree atrioventricular block (AVB) in the Cardiovascular Hospital of Xiamen University from April to December 2019 were selected as pacing group, which were further divided into two groups according to different pacemaker modes: twenty patients with right ventricular septal pacing (RVSP), twenty-two patients with LBBP, and twenty patients with normal ECG and cardiac structure were enrolled as control group. Echocardiography of pacing group and control group was performed and analyzed. The left ventricular subendocardial longitudinal strain peak(LSendo), the middle layer myocardial longitudinal strain peak(LSmid), subepicardial longitudinal strain peak(LSepi), global myocardial longitudinal strain peak(GLS), peak strain dispersion (PSD), global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were acquired. The differences among the three groups were analyzed and the high difference indexes were screened by statistical modeling.Results:LSendo in three groups had no difference ( P>0.05). LSmid, LSepi, GLS in the control group, LBBP group and RVSP groups were decreased gradually ( P<0.05). GLS in LBBP group was higher than in RVSP group ( P<0.05). Compared with the control group, the increases of QRS and PSD in LBBP group were not statistically significant ( P>0.05), while the decreases of QRS and PSD in LBBP group were statistically significant compared with the RVSP group ( P<0.05). The values of GCW among three groups had no statistical significance ( P>0.05). Compared with the control group, the decrease of GWI in LBBP group was not statistically significant ( P>0.05), while the increase of GWW and the decrease of GWE were statistically significant ( P<0.05). Compared with the RVSP group, the increases of GWI and GWE and the decrease of GWW in LBBP group were statistically significant ( P<0.05). QRS, LSendo, GLS, LSmid, left ventricular apex rotation to basal rotation peak time(ApexBase period) were the indexes with significant difference among LBBP and RVSP groups and all index characteristics showed better in LBBP than RVSP group. Conclusions:Two-dimensional multi-layered speckle tracking imaging can be used to evaluate the effect of LBBP on left ventricular systolic function and global synchronization and myocardial work. LBBP longitudinal mechanical synchronization is better than right ventricular septal pacing by improving the peak global myocardial longitudinal strain and myocardial work after pacemaker.

Objectives: To explore and summarize the beneficial effects of a traditional Chinese medicine prepara-tion, Tripterygium glycosides tablets (TGT), in rheumatoid arthritis (RA) animal models of neo-vascularization, and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods: We searched the databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wan Fang and SinoMed (China Biomedical Document Service System) to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April 2020. Subgroup analysis and meta-regression were performed for dosage and duration of TGT. Statistical tests and subgroup analysis were conducted using RevMan 5.3, and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0. Results: Fourteen studies of TGT in RA rats were included in this analysis. Treatment with TGT signifi-cantly reduces synovial microvessel density and the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia inducible factor α, c-Fos, c-Jun, angiopoietin-1 and angiopoietin-2 compared with control groups (P < .05). Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium, assessed using quantitative real-time PCR, with duration or dosage of TGT. Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels. Sensitivity analysis on VEGF mRNA levels did not fundamentally change the results. Conclusions: TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF, VEGF receptor 2, hypoxia-inducible factorα, c-Fos, c-Jun, Ang-1 and Ang-2, thereby suppressing pannus formation and bone destruction in rat models of RA. Additional well-designed studies are required to confirm these findings.

Objective To assess the association between rs7597593 polymorphism of ZNF804A gene and schizophrenia,and to assess the relationship between rs7597593 polymorphism and working memory.Methods Schizophrenia patients and healthy controls were diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-Ⅳ) ; 767 schizophrenia patients and 690 healthy controls were involved.Restriction fragment length polymorphism (RFLP) was carried out to genotype rs7597593 polymorphism.The cognitive function of working memory was assessed by the N-back task.Statistical analyses were carried out with SPSS19.0 software.Results The study found no significantly different genotype frequencies (x2=1.519,P=0.468) and allele frequencies(x2=1.263,P=0.261) of rs7597593 polymorphism between schizophrenia patients and healthy controls,however in the subgroup of higher IQ (IQ ≥ 110),there were significant different distributions of both genotype and allele (x2 =9.411 and 6.529; P=0.009 and 0.011 respectively).It was also found in this subgroup that risk T allele was associated with more error at 1-back task (F=6.854,P=0.009).Conclusion These results indicated that rs7597593 polymorphism was associated with individuals having spared cognitive function; carriers of T allele had worse cognitive function,which maybe a pathway that it contributes to schizophrenia.