Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective To investigate the factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.

BACKGROUND:Slow bone repair and poor bone formation quality are still problems during masquelet technique in the treatment of large segment bone defects.H-type vessels can induce osteogenesis,enhance the local angiogenesis and osteogenesis coupling,and promote bone repair.However,there are few reports on the role of H-type blood vessels in the bone induced membrane.OBJECTIVE:To construct a large segment bone defect model of SD rat tibia,observe the expression characteristics of H-type blood vessels in the bone induced membrane,then to identify the expression peak point of H-type blood vessels in the bone induced membrane and determine the optimal period of bone grafting.METHODS:Sixty SD rats were randomly divided into a control group(n=30)and a model group(n=30)by random number table method.The two groups were further divided into three subgroups at 4,6,and 8 weeks after bone cement implantation,with 10 rats in each group.A 4 mm bone defect model of the right tibia was constructed in both the control and the model groups.Polymethyl methacrylate bone cement was implanted in the model group to induce bone biomembrane formation,while bone cement was not implanted in the control group.At 4,6,and 8 weeks after bone cement implantation,6 rats were randomly selected at each time point.The bone induction membrane tissue was cut from the model group,and the non-bone soft tissue of the corresponding part was cut from the control group.The dynamic expressions of H-type blood vessels in the bone induced membrane were identified by immunofluorescence.The morphological changes of the bone induced membrane were observed by hematoxylin-eosin staining.The formation of blood vessels in the bone induced membrane was observed by angiography.The expression levels of osteoblast-specific transcription factor in the bone induced membrane were detected by immunohistochemistry.Four rats remained at each time point.In the model group,the bone induced membrane was cut open and the bone cement was removed and autologous coccyx was implanted.In the control group,autologous coccyx was implanted in the bone defect area.Micro-CT evaluation of the tibial defect was performed 8 weeks after bone grafting.RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that the expression of H-type vessels in the model group was most obvious 6 weeks after bone cement implantation,and the expression of H-type vessels in the model group at each time point after bone cement implantation was higher than that in the control group(P＜0.05).(2)Hematoxylin-eosin staining and angiography showed that the number and volume of new blood vessels at each time point after bone cement implantation in the model group were greater than those in the control group(P＜0.05).The order of the number and volume of new blood vessels in the model group was:8 weeks after bone cement implantation＞6 weeks after bone cement implantation＞4 weeks after bone cement implantation.(3)Immunohistochemical staining showed that the positive expression of osteoblast-specific transcription factors at each time point after bone cement implantation in the model group was higher than that in the control group(P＜0.05),and the positive expression of osteoblast-specific transcription factors in the model group was most obvious 6 weeks after bone cement implantation.(4)Micro-CT detection showed that the bone repair effect of the three subgroups in the model group was significantly better than that of the corresponding subgroups in the control group,and the bone repair effect of the subgroup in the model group 6 weeks after bone cement implantation was better than that of the subgroups 4 and 8 weeks after bone cement implantation.The results indicate that H-type blood vessels are dynamically expressed in the bone induced membrane and reached a peak 6 weeks after bone cement implantation.Good bone repair effects can be obtained by the bone induced membrane bone grafting 6 weeks after bone cement implantation.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.