In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.