Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.
Female ; Humans ; Atrioventricular Block/therapy* ; Feasibility Studies ; Transcatheter Aortic Valve Replacement ; Pacemaker, Artificial ; Bundle-Branch Block

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Yu Weihan, academician of the Chinese Academy of Engineering, devoted his whole life to the prevention and control of endemic diseases and basically eradicated the epidemic of Keshan disease. Academician Yu Weihan’s struggle experience has left us with valuable spiritual wealth. His spiritual strength is manifested in many aspects, such as the spirit of bearing hardships first, the spirit of innovative daring to be the first, the spirit of craftsmen striving for perfection, the patriotic spirit of caring for the people, and the dedication of being indifferent to fame and wealth. His great medical feelings of bravely shouldering the mission, caring for the people and taking root in the grass-roots have forcefully answered the three important questions: what kind of doctor to be, who to be and how to be a good doctor in the learning and working career of doctors in the new era. He set an model for doctors in later generations and highlighted the value of this spiritual strength for the time.

Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion Multimodal MRI could be used to monitor short-term brain changes in ALS patients.
Adult ; Amyotrophic Lateral Sclerosis ; diagnostic imaging ; physiopathology ; Brain ; diagnostic imaging ; Cerebrovascular Circulation ; Disease Progression ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Multimodal Imaging ; methods ; Prospective Studies

The present study was designed to isolate and characterize the analgesic compounds of Artemisa sacrorum Ledeb. The EtOAc crude extracts from the aerial parts of Artemisa sacrorum Ledeb were separated by chromatography and the structures of new compounds were elucidated based on spectral analyses. Analgesic activities of the isolated compounds were assessed in rats with hot plate test and paw pressure assay. Two new flavone C-glycosides, named as Sacroroside A and B (Compounds 1 and 2) were isolated from the EtOAc crude extract of the aerial parts ofArtemisa sacrorum Ledeb. They showed significant analgesic effects. In conclusion, Compounds 1 and 2 are new natural products, which show significant analgesic effects in a dose-dependent manner.
Analgesics ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Animals ; Artemisia ; chemistry ; Disaccharides ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Flavanones ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Flavones ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Hot Temperature ; Male ; Molecular Structure ; Pain ; drug therapy ; Phytotherapy ; Plant Components, Aerial ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Pressure ; Rats, Wistar

OBJECTIVETo investigate the analgesic and sedative effects of inhaling a mixture of nitrous oxide and oxygen on burn patient during and after dressing change.

METHODSA total of 240 burn patients hospitalized in the Institute of Burn Research of Changhai Hospital Affiliated to the Second Military Medical University, Department of Burns of the First People's Hospital in Zhengzhou, and Department of Burns and Plastic Surgery of General Hospital of Ningxia Medical University from October 2011 to September 2012 were enrolled in our study, and they were all in accordance with the inclusion criteria. The 240 patients were divided into control group (n = 60, treated with inhalation of oxygen during dressing change) and treatment group (n = 180, treated with inhalation of a mixture of 65% nitrous oxide and oxygen during dressing change) according to the computer-generated list of random number. The other treatments in control group and treatment group were the same. Before, during, and after dressing change, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SO2), and adverse effects were observed. The degree of pain and anxiety felt by the patients were respectively evaluated with the visual analogue scale (VAS) and Chinese version of the burn specific pain anxiety scale (C-BSPAS) at the same time points as above. Data were processed with analysis of covariance, chi-square test, analysis of variance, and rank sum test.

RESULTSThere were no significant differences between control group and treatment group in the levels of HR, SBP, DBP, and SO2 before dressing change (with F values respectively 0.76, 0.06, 1.11, 0.70, P values all above 0.05). Compared with those of control group, the levels of HR, SBP, DBP, and SO2 in treatment group were significantly ameliorated during dressing change (with F values respectively 81.78, 146.36, 226.44, 205.62, P values all below 0.01). After dressing change, the levels of DBP in the two groups were close (F = 0.31, P > 0.05), but the levels of HR, SBP, and SO2 showed statistical differences (with F values respectively 7.02, 8.69, 12.23, P < 0.05 or P < 0.01). Before dressing change, the VAS scores were approximate between control group and treatment group (Z = 0.21, P > 0.05). Compared with those in control group (9.4 ± 0.7, 1.7 ± 2.5), the VAS scores were significantly lowered in treatment group during and after dressing change (1.6 ± 1.3, 0.7 ± 1.1, with Z values respectively 11.84, 3.35, P values all below 0.01). There was no significant difference in C-BSPAS score between control group and treatment group before dressing change (Z = 0.62, P > 0.05). Compared with those in control group (75 ± 13, 73 ± 12), the C-BSPAS scores in treatment group were decreased during and after dressing change (9 ± 15, 9 ± 14, with Z values respectively 11.91, 12.28, P values all below 0.01). There were no obvious adverse effects in two groups before, during, and after dressing change.

CONCLUSIONSA mixture of nitrous oxide and oxygen seems to have obvious analgesic and sedative effects on burn patients during dressing change, and it can be widely used.

Administration, Inhalation ; Adolescent ; Adult ; Aged ; Analgesia ; methods ; Bandages ; Burns ; surgery ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Nitrous Oxide ; administration & dosage ; therapeutic use ; Oxygen ; administration & dosage ; therapeutic use ; Young Adult