Abstract Adverse childhood experiences (ACEs) exposure is a pressing and severe global public health issue. Children and adolescents exposed to multiple ACEs are highly susceptible to toxic stress and impaired physiological functioning, which significantly jeopardize their physical and mental health. Effective prevention and intervention strategies can reduce the prevalence of ACEs and mitigate their severe impacts, thereby minimizing the long term detrimental consequences on future outcomes. The review provides a comprehensive review of intervention strategies across four dimensions: individual, family, school, and public services/policy, so as to establish a theoretical foundation for implementing effective interventions for children and adolescents exposed to adverse childhood experiences.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective: To conduct screening for rare blood types within important blood group systems for the Chinese population, such as Rh, Duffy, Kidd, P1Pk, Diego, and MNS, in the Guangzhou region, and to establish a corresponding rare blood type database and physical repository. Methods: The saline medium microplate method was used to screen blood donors with the ccDEE phenotype combined with either Jk(a-) or Jk(b-). The polybrene microplate method was employed to screen for donors with Fy(a-), s(-), Lu(b-), Di(b-), k(-), and p phenotypes. The urea lysis microplate method was applied to screen for the Jk(a-b-) phenotype. A high-resolution melting (HRM) curve method was established for screening some donors with the Di(b-) phenotype. Subsequently, expanded phenotyping of antigens in the Rh, Kidd, MNS, Duffy, P1Pk, Lewis, Kell, and Lutheran blood group systems was performed on identified rare blood type donors using monoclonal antibodies. The test results are entered into the Rare Blood Type Bank Management System of the Guangzhou Blood Center, enabling functions such as confirmation reminders and cryopreservation storage when the donor donates again. Red blood cells of rare blood types are processed into frozen red blood cells for long-term storage. Results: Among voluntary blood donors, 16 cases of the ccDEE combined with Jk(a-) phenotype were identified (0.221 7%, 16/7 216); 10 cases of the ccDEE combined with Jk(b-) phenotype (0.138 6%, 10/7 216); 78 cases of the Fy(a-) phenotype (0.169 5%, 78/46 012); 39 cases of the Lu(b-) phenotype (0.138 2%, 39/28 214); 31 cases of the s(-) phenotype (0.081 8%, 31/37 913); 22 cases of the Di(b-) phenotype (0.029 9%, 22/73 691); 30 cases of the Jk(a-b-) phenotype (0.010 1%, 30/298 250); and 1 case of the k(-) phenotype (0.001 3%, 1/77 382), which was further identified as KELnull phenotype (K0). No p phenotype donors were identified (0/88 528). A total of 228 units of frozen red blood cells were prepared. The screening results were compared and analyzed with rare blood type data from other regions. Conclusion: This study, through a combination of different screening methods, significantly improved the efficiency of rare blood type screening while remaining cost-effective. By conducting large-scale screening and performing data informatization processing, a database and physical repository of rare blood types in the Guangzhou region were successfully established. This provides a strong guarantee for the timely supply of blood to patients with difficult-to-match and rare blood types in the region, effectively enhances the level of transfusion safety in the region, and offers a practical paradigm for constructing a comprehensive blood transfusion support system.

OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

Objective:To analyze the chromosome status of pre-implantation embryos from women of different ages, and assess the impact of age on it.Methods:A retrospective analysis was carried out on the results of PGT-A and PGT-M+ PGT-A cycles by whole-genome amplification followed by next generation sequencing at the Second People′s Hospital of Nanning between July 2021 and November 2023. The embryos were divided into five groups based on the women′s age: ≤ 30 years old group, 31 ~ 34 years old group, 35 ~ 37 years old group, 38 ~ 40 years old group, and ≥ 41 years old group. The chromosomal status of embryos for each group was compared. This study has been approved by the Ethic Committee of the Hospital (Ethics No. Y2024312A).Results:This study has involved 390 couples and 436 PGT cycles, with a total of 1 651 blastocysts biopsied and analyzed. Among these, 835 embryos (50.6%) were found to have chromosomal abnormalities, including 490 (29.7%) with aneuploidies, 154 (9.3%) with chromosomal segment abnormalities, and 264 (16.0%) with chromosome mosaicisms. After adjusting the dosages of Gn, female BMI, male age, PGT indications, infertility type, LH, AMH and other parameters, maternal age appeared to be an independent factor for chromosomal abnormalities and aneuploidies in blastocysts ( OR=1.132, 95% CI = 1.089 - 1.177, P<0.001; OR=1.250, 95% CI = 1.188-1.315, P<0.001). With the increase in female age, embryonic chromosome abnormalities have significantly increased in each group, with the rates being 32.3% (126/390), 43.1% (189/439), 45.1% (116/257), 66.3% (250/377), and 81.9% (154/188) ( P<0.001). Chromosomal aneuploidies have also significantly increased, with the rates being 8.2% (32/390), 16.6% (73/439), 24.5% (63/257), 49.6% (187/377), and 71.8% (135/188) ( P<0.001). The proportion of embryos with ≥ 2 chromosome abnormalities also significantly increased in abnormal embryos, with the rates being 28.6% (36/126), 30.2% (57/189), 39.7% (46/116), 48.4% (121/250), and 64.9% (100/154) ( P<0.001). Of note, the female age did not affect the prevalence of chromosomal segment abnormalities and mosaicisms (all P>0.05). Conclusion:The findings suggested that along with the increase infemale age, there was an increase in the rate of chromosomal abnormalities, at the same time, the type of chromosomal abnormality changed, mainly with an increased incidence of chromosomal aneuploidy, and the proportion of embryos involving multiple chromosomal abnormalities increases significantly.

Carotid ultrasound is the primary imaging modality for evaluating carotid artery diseases.In recent years,novel ultrasound techniques such as pulse wave velocity imaging,shear wave elastography,superb microvascular imaging,three-dimensional ultrasound and contrast-enhanced ultrasound,have been employed in assessment of carotid pathologies,providing important evidences for clinical diagnosis and prognostic evaluation.The progresses of clinical applications of carotid ultrasound were reviewed in this article.

Objective:To explore the association between healthy lifestyle and co-morbidity of overweight/obesity and myopia in adolescents.Methods:Based on the Shanghai Municipal Dynamic Cohort of Student Common Diseases, we used the group-based trajectory model (GBTM) to establish a model for the development of adolescents' healthy lifestyle trajectories aged 11-14 years and the Cox proportional hazard regression model to assess the effects of different healthy lifestyles on the co-morbidity of overweight/obesity and myopia in adolescents.Results:A total of 2 331 adolescents were included in the analysis. The average follow-up time was 1.87 years, with age of (11.44±0.45) years at the initial follow-up, among 1 106 boys and 1 225 girls. During the 2-year follow-up period, the incidence rates of overweight/obesity, myopia, and co-occurrence of overweight/obesity and myopia were 25.9%, 77.0%, and 13.7%, respectively. GBTM identified 3 healthy lifestyles: the unhealthy group (7.3%), the relatively healthy group (50.2%), and the healthy group (42.5%). The risk of overweight/obesity was lower in the relatively healthy group than in the unhealthy group ( HR=0.694, 95% CI: 0.508-0.947). There was no statistically significant association between the GBTM lifestyle subgroups and myopia ( P>0.05). The risk of co-occurrence of overweight/obesity and myopia was lower in both relatively healthy group and healthy group than in the unhealthy group (relatively healthy group: HR=0.515, 95% CI: 0.348-0.763; healthy group: HR=0.571, 95% CI: 0.384-0.849). Sensitivity analyses showed this result to be stable for myopia, overweight/obesity and myopia co-morbidities. Conclusion:Persistent unhealthy lifestyle increases the risk of overweight/obesity and myopia co-occurrence in adolescents.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

Purpose To investigate the diagnostic value of immunohistochemical(IHC)and molecular markers in diffuse pleural mesothelioma(DPM).Methods A total of 114 cases of DPM were retrospectively analyzed for clinical and imaging manifestations,histologic subtype and tumor grade.The positivity rates of Calretinin,WT-1,CK5/6,MC,D2-40,UPK3B,and GATA3 were assessed by IHC,and the loss rates of BAP-1 and MTAP were determined.The concordance between MTAP IHC and p16 gene fluorescence in situ hybridization(FISH)status was calculated,a-long with the sensitivity and specificity of MTAP IHC relative to p16 FISH.Results Among the 114 DPM patients,66(57.9％)were male and 48(42.1％)were female,with a mean age of 58.1 years(range 16-85 years).Imaging predominantly demonstrated pleural effusion and multiple pleural nodules(55.3％,63/114).Histologically,epitheli-oid,sarcomatoid and biphasic subtypes accounted for 88(77.2％),17(14.9％)and 9(7.9％)cases,respectively.Within the epithelioid group,low and high-grade tumors numbered 69(78.4％)and 19(21.6％),respectively.In epithelioid DPM,the highest IHC positivity rates were observed for Calretinin(92.4％,81/88),D2-40(90.0％,79/88)and WT-1(90.0％,79/88).In sarcomatoid DPM,D2-40(76.5％,13/17),WT-1(64.7％,11/17),and Cal-retinin(29.4％,5/17)showed the greatest positivity.UPK3B was positive in epithelioid(59.1％,39/66)and bi-phasic cases(66.7％,4/6),but was absent in sarcomatoid tumors(0/12).Among all DPM cases,loss rates were 47.3％(53/112)for BAP-1 and 19.2％(20/104)for MTAP by IHC,p16 gene deletion by FISH was 31.5％(34/108);Concordance between MTAP IHC and p16 FISH was 81.0％(81/100);MTAP IHC had a specificity of 95.5％(64/67)and sensitivity of 51.5％(17/33)relative to p16 FISH.Additionally,GATA3 was highly expressed in sarco-matoid DPM(76.5％,13/17).UPK3B positivity differed significantly between thoracoscopic DPM(59.2％,32/54)and percutaneous biopsy samples(36.7％,11/30)in epithelioid DPM(P＜0.05).WT-1 positivity was higher in thoracoscopic than percutaneous samples of sarcomatoid DPM(90.0％ vs 28.6％,P=0.009).Conclusion Calreti-nin,D2-40,and WT-1 are highly sensitive mesothelial markers and should serve as first-line IHC stains in DPM diag-nosis.UPK3B is diagnostically valuable in epithelioid DPM,GATA3 may complement the diagnosis of sarcomatoid DPM,and MTAP IHC can be used as a surrogate or adjunct to p16 FISH.

Objective To develop an exercise rehabilitation program for the patients with upper limb lymphedema in order to provide standardised guidance for specialised management and nursing practice,and to promote the recovery of patients.Methods With the evidence-based methods,domestic and international literaturs were retrieved and the quality of the papers was evaluated.A research team was established to discuss and draft an initial version of the rehabilitation program for the patients with upper limb lymphedema.Delphi method was used to conduct two rounds of consultation with 15 experts in lymphedema between June and September 2023.According to the expert opinions,the exercise rehabilitation program for patients with upper limb lymphedema was finalised after screening and modification of the indicators.Results The final version of the exercise rehabilitation program for patients with upper limb lymphedema includes four tier-1 indicators(routine upper limb rehabilitation exercises,aerobic exercise,anti-resistance exercise and respiratory training),15 tier-2 indicators,and 33 tier-3 indicators.The positive response rate in both rounds of expert consultation was 100.00%,with the authority coefficient at 0.95.In the second round of expert consultation,it was founds that the importance of tier-3 indicators was from 3.93 to 5.00,with the rationality from 4.13 to 5.00 and the feasibility from 3.53 to 4.93.The coefficient of variation in tier-1 and tier-2 indicators was 0.00-0.17 and 0.07-0.23,respectively.The coefficients of variation of per tier-3 indicator in importance,rationality and feasibility were from 0.00 to 0.22,0.00 to 0.22 and 0.05 to 0.22,respectively.The Kendall's coefficient of concordance(W)for tier-1 and tier-2 indicators was 0.490 and 0.387,respectively.The Kendall's W of per tier-3 indicator in importance,rationality and feasibility was 0.427,0.311 and 0.530,respectively,with statistically significant differences(P<0.001).Conclusion The exercise rehabilitation program developed in this study is scientific,comprehensive and highly targeted.It provides a theoretical basis and practical guidance for exercise rehabilitation and nursing care of the patients with upper limb lymphedema.