Treatment of recurrent trigeminal neuralgia after microvascular decompression: How to select.

BACKGROUND: This study aimed to investigate individualized treatment strategies and clinical outcomes in patients with recurrent trigeminal neuralgia after undergoing microvascular decompression (MVD). METHODS: One hundred forty-four patients with recurrent trigeminal neuralgia after MVD were retrospectively examined and grouped according to treatment. Surgical efficacy and pain recurrence were analyzed as outcomes. RESULTS: Repeat craniotomy was performed in 31 patients (21.5 %), percutaneous balloon compression (PBC) in 67 (46.5 %), and radiofrequency thermocoagulation (RFT) in 46 (32.0 %). Effectiveness did not differ among the three types of treatment (P = 0.052). The incidence of postoperative complications, including trigeminal nerve cardiac reflex, facial numbness, and mastication weakness, was lower in the craniotomy group than the PBC and RFT groups (P < 0.001). The 5-year pain recurrence rate was significantly higher than the 1-year rate in all groups. Although the 1-year pain recurrence rate did not differ among the groups, the 5-year rate was significantly lower in the repeat craniotomy group than the other groups (P < 0.001). CONCLUSION: Patients with recurrent trigeminal neuralgia after MVD should be treated based on imaging evaluation and general condition. Repeat craniotomy, PBC, and RFT are all effective. Incidence of postoperative complications and long-term pain recurrence-free survival are superior for repeat craniotomy.

Comparison of efficacy and safety between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma.

Aims and objectives: The purpose of this study was to compare efficacy and side effects between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma (IH). Material and methods: This was a single center randomized controlled prospective study, all participants were firstly diagnosed with IH between August 2022 and January 2023 in our hospital and without any treatment before. Patients were randomized into two groups. PRO group: oral propranolol (2 mg/kg/day) continued for 6 months; PRO + LAU group: oral propranolol (2 mg/kg/day) for 6 months and intralesional injection of lauromacrogol for 2-4 times within 6 months. The dimensions, color, consistency, photographic documentation were well recorded based on Visual Analogue Scale (VAS) before and after starting treatment. According to the treatment response after 6 months, the results were classified into four levels: Grade 1, complete resolution achieved; Grade 2, with ≥50% reduction in size of IH; Grade 3, with <50% reduction in size of IH; Grade 4, no response or worsening of IH. Results: A total of 67 patients were involved in the study (17 boys, 50 girls; mean age, 3.6 months, range, 1.1-7.2 months) and randomized to receive oral propranolol combined with or without intralesional injection of lauromacrogol (29 in PRO group, 38 in PRO + LAU group). All patients completed treatment. Eleven patients (37.9%) in PRO group were in Grade 1, 14 patients (48.3%) in Grade 2, 4 patients (13.8%) in Grade 3, compared with these in PRO + LAU group, 11 patients (28.9%) in Grade 1, 24 patients (63.2%) in Grade 2, and 3 patients (7.9%) in Grade 3. No patient was in Grade 4, and no severe side effects were observed in both group. In PRO group, it takes an average of 17.1 ± 5.4 weeks from the start of treatment to cure, and in PRO + LAU group, the average time is 13.7 ± 4.9 weeks. Conclusion: Oral propranolol with intralesional injection of lauromacrogol was a safety treatment strategy for IH. But it was not superior to oral propranolol in final cure rates (P = 0.45), moreover, it cannot certainly offer the benefits of shortening the duration of oral drug treatment (P = 0.24).

Case Report: unexpected cause of cyanosis in an infant after acute exposure to high altitude-severe tricuspid regurgitation secondary to tricuspid valve prolapse.

Background: Severe tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy. Tricuspid valve prolapse (TVP) can lead to TR and is sometimes overlooked, especially in complex cases with factors like pulmonary hypertension (PH). We present an infant with cyanosis and profound TR after high-altitude exposure, initially misattributed to PH but found to be primarily due to spontaneous chordae tendineae rupture and TVP. This case underscores the challenges in diagnosing TR-induced cyanosis. Case presentation: The 3-month-old infant rapidly developed cyanosis, hypoxemia, right atrial enlargement, severe tricuspid regurgitation (TR), and patent foramen ovale (PFO) shunting after high-altitude exposure. Although echocardiography revealed tricuspid valve prolapse (TVP), initial consideration linked TR and right-to-left shunting to pulmonary hypertension (PH) due to the temporal correlation with rapid altitude exposure. Despite hemodynamic stability and the absence of respiratory distress after respiratory support and combined PH medication therapy, the persistent hypoxemia did not reverse as expected. This treatment outcome and repeated echocardiograms reminded us that TR was primarily caused by TVP rather than PH alone. Intraoperative exploration confirmed that TVP was caused by a rupture of TV chordae tendineae and anterior papillary muscle head, and the chordae tendineae/papillary muscle connection was reconstructed. After surgery, this patient was noncyanotic with an excellent long-term prognosis, a trivial TR with normal TV function being observed echocardiographically. Conclusions: TR-induced cyanosis can be not only a consequence of PH and right-sided heart dilation but also a primary condition. Repetitive reassessment should be undertaken with caution, particularly when patients are not improving on therapy in the setting of conditions known to predisposition to secondary TR. Since TVP caused by rupture of the chordae or papillary muscles is rare but fatal in children, early diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.

Unlocking the Medicinal Potential of Plant-Derived Extracellular Vesicles: current Progress and Future Perspectives.

Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.

Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review.

INTRODUCTION: Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the KIT gene. METHODS: Four KIT variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype-phenotype correlation was summarized through extensive literature reviewing. RESULTS: All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the KIT gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease. CONCLUSION: Our data expand the mutation spectrum of KIT, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.

[Expert consensus on the genetic counseling for Dystrophinopathies].

Dystrophinopathies caused by variants of DMD gene are a group of muscular diseases including Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy. With the advancement of genetic testing techniques and wider implementation of genetic screening, especially the expanded carrier screening, more and more individuals carrying DMD gene variants have been identified, whereas the genetic counseling capacity is relatively insufficient. Currently there is still a lack of professional norms for genetic counseling on dystrophinopathies. In this consensus, the main points to be covered in the pre- and post-test consultation have been discussed, with an aim to provide genetic counseling guidance for the disease diagnosis, treatment, and family reproduction.

Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.

Combination of metagenomic next-generation sequencing and conventional tests unraveled pathogen profiles in infected patients undergoing allogeneic hematopoietic stem cell transplantation in Jilin Province of China.

Background: Infection is the main cause of death for patients after allogeneic hematopoietic stem cell transplantation (HSCT). However, pathogen profiles still have not been reported in detail due to their heterogeneity caused by geographic region. Objective: To evaluate the performance of metagenomic next-generation sequencing (mNGS) and summarize regional pathogen profiles of infected patients after HSCT. Methods: From February 2021 to August 2022, 64 patients, admitted to the Department of Hematology of The First Hospital of Jilin University for HSCT and diagnosed as suspected infections, were retrospectively enrolled. Results: A total of 38 patients were diagnosed as having infections, including bloodstream (n =17), pulmonary (n =16), central nervous system (CNS) (n =4), and chest (n =1) infections. Human betaherpesvirus 5 (CMV) was the most common pathogen in both bloodstream (n =10) and pulmonary (n =8) infections, while CNS (n =2) and chest (n =1) infections were mainly caused by Human gammaherpesvirus 4 (EBV). For bloodstream infection, Mycobacterium tuberculosis complex (n =3), Staphylococcus epidermidis (n =1), and Candida tropicalis (n =1) were also diagnosed as causative pathogens. Furthermore, mNGS combined with conventional tests can identify more causative pathogens with high sensitivity of 82.9% (95% CI 70.4-95.3%), and the total coincidence rate can reach up to 76.7% (95% CI 64.1-89.4%). Conclusions: Our findings emphasized the importance of mNGS in diagnosing, managing, and ruling out infections, and an era of more rapid, independent, and impartial diagnosis of infections after HSCT can be expected.

odd skipped-related 2 as a novel mark for labeling the proximal convoluted tubule within the zebrafish kidney.

The proximal convoluted tubule (PCT) of the kidney is a crucial functional segment responsible for reabsorption, secretion, and the maintenance of electrolyte and water balance within the renal tubule. However, there is a lack of a well-defined endogenous transgenic line for studying PCT morphogenesis. By analyzing single-cell transcriptome data from the adult zebrafish kidney, we have identified the expression of odd-skipped-related 2 (osr2, which encodes an odd-skipped zinc-finger transcription factor) in the PCT. To gain insight into the role of osr2 in PCT morphogenesis, we have generated a transgenic zebrafish line Tg(osr2:EGFP), expressing enhanced green fluorescent protein (EGFP). The EGFP expression pattern closely mirrors that of endogenous Osr2, faithfully recapitulating its native expression profile. During kidney development, we can use EGFP to track PCT development, which is also preserved in adult zebrafish. Additionally, osr2:EGFP-labeled zebrafish PCT fragments displayed short lengths with infrequent overlap, rendering them conducive for nephrons counting. The generation of Tg(osr2:EGFP) transgenic line is accompanied by simultaneous disruption of osr2 activity. Importantly, our findings demonstrate that osr2 inactivation had no discernible impact on the development and regeneration of Tg(osr2:EGFP) zebrafish nephrons. Overall, the establishment of this transgenic zebrafish line offers a valuable tool for both genetic and chemical analysis of PCT.

Treatment Options for Distal Rectal Cancer in the Era of Organ Preservation.

OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.

Evaluation of left ventricular stiffness with echocardiography.

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography-derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end-diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure-volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time-velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography-derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness.

Using nomogram scores to predict the early regression of coronary artery aneurysms of Kawasaki disease.

BACKGROUND: Coronary artery aneurysms have been considered the most serious complication of Kawasaki disease. However, some coronary artery aneurysms do regress. Therefore, the ability to predict the expected time of coronary artery aneurysm regression is critical. Herein, we have created a nomogram prediction system to determine the early regression (<1 month) among patients with small to medium coronary artery aneurysms. METHODS: Seventy-six Kawasaki disease patients identified with coronary artery aneurysms during the acute or subacute phase were included. All the patients who met inclusion criteria demonstrated regression of coronary artery aneurysms within the first-year post Kawasaki disease diagnosis. The clinical and laboratory parameters were compared between the groups of coronary artery aneurysms regression duration within and beyond 1 month. Multivariate logistic regression analysis was used to identify the independent parameters for early regression based on the results from the univariable analysis. Then nomogram prediction systems were established with associated receiver operating characteristic curves. RESULTS: Among the 76 included patients, 40 cases recovered within 1 month. Haemoglobin, globulin, activated partial thromboplastin time, the number of lesions, location of the aneurysm, and coronary artery aneurysm size were identified as independent factors for early regression of coronary artery aneurysms in Kawasaki disease patients. The predictive nomogram models revealed a high efficacy in predicting early regression of coronary artery aneurysms. CONCLUSION: The size of coronary artery aneurysms, the number of lesions, and the location of aneurysms presented better predictive value for predicting coronary artery aneurysms regression. The nomogram system created from the identified risk factors successfully predicted early coronary artery aneurysm regression.

Clinical and genetic profiles of chinese pediatric patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUNDS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. AIMS AND METHODS: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. RESULTS: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. CONCLUSION: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.

Risk Factors for Nodal Failure in Patients with FIGO IIIC Cervical Cancer Receiving Definitive Image-Guided Radiotherapy.

BACKGROUND: Nodal failure is a major failure pattern for patients with FIGO IIIC cervical cancer, which is further associated with worse survival. This study was designed to investigate risk factors for nodal failure in FIGO IIIC cervical cancer patients. METHODS: The characteristics of positive lymph nodes (LNs) and relevant clinical factors of 162 FIGO IIIC cervical cancer patients were collected. The chi-square test and logistic regression model were used to identify risk factors for nodal failure. RESULTS: In total, 368 positive LNs were identified, including 307 pelvic LNs and 61 para-aortic LNs. The nodal failure rates for all LNs, pelvic LNs, and para-aortic LNs were 9.2%, 7.8%, and 16.4%, respectively. After 20 fractions of RT, a nodal short diameter (D20F) ≥ 0.95 cm and a ratio of nodal shrinkage (ΔV20F) < 0.435 resulted; <4 cycles of chemotherapy indicated higher nodal failure rates for all LNs. For pelvic LNs, ΔV20F < 0.435 and <4 cycles of chemotherapy were associated with a higher incidence of nodal failure. For para-aortic LNs, ΔV20F < 0.435 was the only risk factor for nodal failure. CONCLUSIONS: Para-aortic LNs were more likely to experience nodal failure than pelvic LNs. Nodal shrinkage during radiotherapy and cycles of chemotherapy were associated with nodal failure in patients with FIGO IIIC cervical cancer.

Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration.

Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.

Coronary artery dilation in children with febrile illnesses other than Kawasaki disease: A case report and literature review.

Background: Coronary artery dilation (CAD) had rarely been described as a cardiac complication of febrile disease other than Kawasaki disease (KD). There are rare cases complicated by CAD reported in patients with Mycoplasma pneumoniae (MP) infection. Case presentation: A 6-year-old boy with severe Mycoplasma pneumoniae pneumonia (MPP) was transferred to our hospital due to significant respiratory distress on the 11th day from disease onset. Nadroparin, levofloxacin, and methylprednisolone followed by oral prednisone were aggressively prescribed. His clinical condition gradually achieved remission, and the drugs were withdrawn on the 27th day. Regrettably, the recurrent fever attacked him again in the absence of infection-toxic manifestations. Necrotizing pneumonia (NP) was found on chest CT. And echocardiography revealed right CAD (diameter, 3.40mm; z-score, 3.8), however, his clinical and laboratory findings did not meet the diagnostic criteria of KD. CAD was proposed to result from MP infection, and aspirin was prescribed. Encouragingly, the CAD regressed one week later (diameter, 2.50mm; z-score, 1.4). Additionally, the child defervesced seven days after the initiation of prednisone and Nadroparin treatment. The patient was ultimately discharged home on the 50th day. During follow-up, the child was uneventful with normal echocardiography and fully resolved chest CT lung lesions. Conclusions: CAD can develop in patients with severe MP infection. Pediatricians should be alert to the possibility of CAD in patients with severe MP infection and recognize that CAD might also develop in febrile disease rather than KD.

Autologous hematopoietic recovery after allogeneic hematopoietic stem cell transplantation: A case-based review.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely applied for the treatment of hematologic malignancies, but autologous hematopoietic recovery (AR) after allo-HSCT is rare clinically, especially after myeloablative conditioning (MAC). The mechanism of AR remains unclear so far, but the prognosis for most patients is relatively good. Second transplantation is preferred after disease relapse. Starting from a real-life clinical case scenario, herein we reviewed some of the crucial issues of AR in light of recent refinements, and discussed our patients based on the current evidence.

Nacre-mimetic cerium-doped nano-hydroxyapatite/chitosan layered composite scaffolds regulate bone regeneration via OPG/RANKL signaling pathway.

Autogenous bone grafting has long been considered the gold standard for treating critical bone defects. However, its use is plagued by numerous drawbacks, such as limited supply, donor site morbidity, and restricted use for giant-sized defects. For this reason, there is an increasing need for effective bone substitutes to treat these defects. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable "brick-and-mortar" architecture. Inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). Hydroxyapatite can provide a certain strength to the material like a brick. And as a polymer material, chitosan can slow down the force when the material is impacted, like an adhesive. As seen in natural nacre, the combination of these inorganic and organic components results in remarkable tensile strength and fracture toughness. Cerium ions have been demonstrated exceptional anti-osteoclastogenesis capabilities. Our scaffold featured a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 µm, which provided a conducive environment for human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, allowing for in situ growth of newly formed bone tissue. In vitro, Western-blot and qPCR analyses showed that the CeHA/CS layered composite scaffolds significantly promoted the osteogenic process by upregulating the expressions of osteogenic-related genes such as RUNX2, OCN, and COL1, while inhibiting osteoclast differentiation, as indicated by reduced TRAP-positive osteoclasts and decreased bone resorption. In vivo, calvarial defects in rats demonstrated that the layered CeHA/CS scaffolds significantly accelerated bone regeneration at the defect site, and immunofluorescence indicated a lowered RANKL/OPG ratio. Overall, our results demonstrate that CeHA/CS scaffolds offer a promising platform for bone regeneration in critical defect management, as they promote osteogenesis and inhibit osteoclast activation.