Ovulation-induced frozen embryo transfer regimens in women with polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: To evaluate whether the type of frozen embryo transfer (FET) regimen - ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) - is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS). METHODS: All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP. RESULTS: Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59-0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different. CONCLUSION: This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens.

Advances in the Construction and Application of Thyroid Organoids.

Organoids are complex multicellular structures that stem cells self-organize in three-dimensional (3D) cultures into anatomical structures and functional units similar to those seen in the organs from which they originate. This review describes the construction of thyroid organoids and the research progress that has occurred in models of thyroid-related disease. As a novel tool for modeling in a 3D multicellular environment, organoids help provide some useful references for the study of the pathogenesis of thyroid disease.

[Clinicopathological and molecular diagnostic features of early-onset gastric cancer: a study based on data from a single-center dedicated gastric cancer database].

Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Short-term outcome of patients after transcatheter aortic valve replacement receiving different anticoagulants].

Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.

[Expression changes of NaV channel subunits correlate with developmental maturation of electrophysiological characteristics of rat cerebellar Purkinje neurons].

OBJECTIVE: To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons. METHODS: We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development. RESULTS: The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05). CONCLUSION: The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

Research progress into adipose tissue macrophages and insulin resistance.

In recent years, there has been an increasing incidence of metabolic syndrome, type 2 diabetes, and cardiovascular events related to insulin resistance. As one of the target organs for insulin, adipose tissue is essential for maintaining in vivo immune homeostasis and metabolic regulation. Currently, the specific adipose tissue mechanisms involved in insulin resistance remain incompletely understood. There is increasing evidence that the process of insulin resistance is mostly accompanied by a dramatic increase in the number and phenotypic changes of adipose tissue macrophages (ATMs). In this review, we discuss the origins and functions of ATMs, some regulatory factors of ATM phenotypes, and the mechanisms through which ATMs mediate insulin resistance. We explore how ATM phenotypes contribute to insulin resistance in adipose tissue. We expect that modulation of ATM phenotypes will provide a novel strategy for the treatment of diseases associated with insulin resistance.

[Gray zone lymphoma: five cases report and literature review].

Objective: To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) . Methods: From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively. Results: There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission. Conclusions: GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Differences in phenotypes, symptoms, and survival in patients with cardiomyopathy-a prospective observational study from the Sahlgrenska CardioMyoPathy Centre.

Introduction: Cardiomyopathy is the fourth most common cause of heart failure. The spectrum of cardiomyopathies may be impacted by changes in environmental factors and the prognosis may be influenced by modern treatment. The aim of this study is to create a prospective clinical cohort, the Sahlgrenska CardioMyoPathy Centre (SCMPC) study, and compare patients with cardiomyopathies in terms of phenotype, symptoms, and survival. Methods: The SCMPC study was founded in 2018 by including patients with all types of suspected cardiomyopathies. This study included data on patient characteristics, background, family history, symptoms, diagnostic examinations, and treatment including heart transplantation and mechanical circulatory support (MCS). Patients were categorized by the type of cardiomyopathy on the basis of the diagnostic criteria laid down by the European Society of Cardiology (ESC) working group on myocardial and pericardial diseases. The primary outcomes were death, heart transplantation, or MCS, analyzed by Kaplan-Meier and Cox proportional regression, adjusted for age, gender, LVEF and QRS width on ECG in milliseconds. Results: In all, 461 patients and 73.1% men with a mean age of 53.6 ± 16 years were included in the study. The most common diagnosis was dilated cardiomyopathy (DCM), followed by cardiac sarcoidosis and myocarditis. Dyspnea was the most common initial symptom in patients with DCM and amyloidosis, while patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) presented with ventricular arrythmias. Patients with ARVC, left-ventricular non-compaction cardiomyopathy (LVNC), hypertrophic cardiomyopathy (HCM), and DCM had the longest time from the debut of symptoms until inclusion in the study. Overall, 86% of the patients survived without heart transplantation or MCS after 2.5 years. The primary outcome differed among the cardiomyopathies, where the worst prognosis was reported for ARVC, LVNC, and cardiac amyloidosis. In a Cox regression analysis, it was found that ARVC and LVNC were independently associated with an increased risk of death, heart transplantation, or MCS compared with DCM. Further, female gender, a lower LVEF, and a wider QRS width were associated with an increased risk of the primary outcome. Conclusions: The SCMPC database offers a unique opportunity to explore the spectrum of cardiomyopathies over time. There is a large difference in characteristics and symptoms at debut and a remarkable difference in outcome, where the worst prognosis was reported for ARVC, LVNC, and cardiac amyloidosis.

Fine-Tuning of Entangled Two-Photon Absorption by Controlling the One-Photon Absorption Properties of the Chromophore.

The detailed analysis of the sum-over-state formula for the entanglement-induced two-photon absorption (ETPA) transition moment shows that the magnitude of the ETPA cross-section is expected to vary significantly depending on the coherence time Te and the relative position of just two electronic states. Moreover, the dependency on Te is periodic. These predictions are confirmed by molecular quantum mechanical calculations for several chromophores.

[Clinicopathological features and prognostic factors of gastric intermediate-risk gastrointestinal stromal tumor after surgical resection: a retrospective study].

Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.

Genome-wide identification and expression analysis of NAC family genes in Ginkgo biloba L.

NAC (NAM, ATAF, CUC2) transcription factors constitute one of the largest families of plant-specific transcription factors with important roles in plant growth and development and in biotic and abiotic stresses. The physicochemical properties, gene structure, cis-acting elements and expression patterns of NAC transcription factors in Ginkgo biloba were analysed using bioinformatics, and expression of this gene family was analysed via quantitative reverse transcription PCR. The family of G. biloba NAC transcription factors had 50 members, distributed on 12 chromosomes and divided into 11 groups. Members in the same group share a similar gene structure and motif distribution. Transcriptome data analysis of G. biloba showed that 35 genes were expressed in eight tissues. Correlation analysis suggested that GbNAC007 and GNAC008 might be involved in flavonoid biosynthesis. Expression levels of 12 GbNACs under cold, het, and salt stresses were analysed. Results indicate that NAC transcription factors play an important role in response to abiotic stresses. This study provides a reference for the functional analysis of the G. biloba family of NAC transcription factors, as well as a resource for studies on the involvement of this family in responses to abiotic stresses and flavonoid biosynthesis.

Benign submandibular gland tumours: outcomes of gland-preserving excision by endoscopic or conventional approach.

Endoscope-assisted surgery is becoming a preferred technique in salivary gland surgery. However, this technique has not yet been applied in submandibular gland (SMG) preservation surgery. This retrospective study was performed to evaluate the outcomes of endoscope-assisted gland-preserving surgery through a hairline incision in patients with benign SMG tumours. The study included 38 patients with benign SMG tumours who underwent tumour excision with gland preservation: 19 who underwent local excision of the tumour through an endoscope-assisted hairline approach and 19 who received the conventional cervical approach. The feasibility of the surgical procedure, perioperative patient variables, and postoperative appearance and functional outcomes were evaluated. Patients in both groups had their tumours removed successfully with tumour-free margins. The intraoperative blood loss, postoperative amount of drainage, mean length of the incision, and unstimulated saliva flow rate did not differ between the two groups. There was no difference in the stimulated saliva flow rate between the preserved gland and unaffected SMG. The aesthetic result was better in the endoscope-assisted hairline incision group. No tumour recurrence occurred during follow-up (range 12-52 months). Thus, gland-preserving tumour dissection appears to be a safe method for benign SMG tumours, with good functional results. Furthermore, the endoscope-assisted hairline incision is a feasible method with excellent cosmetic results.

[A deep-learning model for the assessment of coronary heart disease and related risk factors via the evaluation of retinal fundus photographs].

Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve (AUC) and R2 correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R2 value of 0.931 (95%CI 0.929-0.933) for monocular photos and 0.938 (95%CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95%CI 0.982-0.984) and 0.988 (95%CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95%CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95%CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.

Data for the Spanish adaptation of Breast Cancer and Lymphedema Symptom Experience Index (BCLE SEI Esp).

Breast cancer is one of the most diagnosed cancer in women worldwide and lymphedema is one of the most common late and chronic adverse effects of breast cancer treatment. Lymphedema symptoms are essential signs of early-stage of lymphedema as they often precede changes in limb size or girth or a lymphedema diagnosis. Therefore, to achieve early detection and prevent lymphedema progression, it is important to promote patient selfcare in terms of the awareness symptoms identification. To this purpose Breast Cancer and Lymphedema Symptom Experience Index (BCLE SEI Esp) scale was used. Between October 2018 and June 2020, we collected data from 286 lymphedema and non-lymphedema patients post-breast cancer treatment on sociodemographic information, lymphedema symptoms, daily living-function and psychosocial distress, women and the data comparison between lymphedema and non-lymphedema patients were provided in this publication. This dataset can be used as a reference in clinical settings or in clinical studies or as an instructional tool to teach breast cancer patients and clinicians to be aware of lymphedema symptoms and to help clinicians and patients to achieve early identification of lymphedema symptoms and the impacts of lymphedema symptoms in women´s life and to develop future research, for example, to develop predictive algorithms.

[The relationship between peripheral blood mitochondrial DNA copy number and incident risk of liver cancer: a case-cohort study].

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (Pnon-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q2 subgroup of mtDNAcn, those in the Q1 subgroup (HR=2.00,95%CI:1.08-3.70) and Q4 subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q3 subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (Pinteraction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.