OBJECTIVE: To carry out pathological and genetic analyses on a fetus with intrauterine growth restriction and death during second trimester after induced abortion. METHODS: A fetus undergone induced abortion due to intrauterine growth restriction and death during second trimester at the the Seventh Affiliated Hospital of Sun Yat-Sen University in 2024 was selected as the study subject. Clinical data of the pregnancy were collected. DNA was extracted from tissues from the aborted fetus and peripheral blood samples from its parents. Chromosomal microarray analysis and whole exome sequencing were carried out. Candidate variants were verified by Sanger sequencing. Following abortion, routine autopsy and pathological analysis were conducted. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: KY-2025-334-01). RESULTS: The aborted fetus was a male and harbored compound heterozygous nonsense variants of the TH gene (c.457C>T/p.Arg153* and c.694C>T/p.Gln232*), for which both parents were heterozygous carriers. Autopsy and pathological analysis revealed that the fetus had pathological features including loose arrangement of myocardial fibers and congestion in the liver. CONCLUSION Biallelic null variants of the TH gene may cause heart failure by affecting the development of cardiovascular system, which in turn may lead to intrauterine death. This study has provided new clues for the molecular diagnosis of stillbirth and recurrent pregnancy loss.
Humans ; Female ; Pregnancy ; Male ; Heterozygote ; Codon, Nonsense/genetics* ; Fetal Growth Retardation/pathology* ; Adult ; Stillbirth/genetics*

Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Background::The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.Methods::A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included. Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0-99.9, 100.0-129.9 [reference group], 130.0-159.9, 160.0-189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality.Results::During a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality ( P for non-linearity <0.001). Compared with the reference group (100.0-129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06-1.14) and HS mortality (HR: 1.37, 95% CI: 1.29-1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40-1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92-2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people. Conclusions::People with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

Objective To propose a double watermarking algorithm based on contourlet transform and speckle detection to automatically select the region of interest(ROI)for solving the problems of copyright infringement and malicious destruction of CT and MRI images.Methods The method used speckle detection and singular value decomposition to select the most relevant location in the low frequency domain of the medical image contourlet wave as the ROI,generated a zero-watermarked image in ROI for protecting image integrity,and embed the ROI zero-watermark and the copyright watermark together in the region of non-interest.Results Compared with other double watermarking algorithms,the double watermarking algorithm could greatly improve the invisibility of the carrier image after the attack.The double watermarked images had a structure similarity index measure higher than 94%.Conclusion The proposed double watermarking algorithm incorporating speckle detection and contourlet transform has better robustness against conventional attacks and geometric attacks,and significantly improves the visual quality of carrier images.

Objective:To explore the application value of dynamic monitoring of serum soluble interleukin-2 receptor (sIL-2R) and stromal cell-derived factor 1 α (SDF-1α) in patients with acute leukemia (AL).Methods:A total of 187 patients with AL admitted to the Second Hospital of Shanxi Medical University from March 2017 to August 2018 were selected and 90 healthy subjects at the same period were selected as the healthy controls. The levels of serum sIL-2R and SDF-1α were detected at the initial diagnosis, remission phase and relapse phase, respectively. The clinical value of dynamic monitoring of sIL-2R and SDF-1α was analyzed.Results:Among 187 patients with AL, 135 patients (72.19%) had complete remission (CR) after chemotherapy, 52 patients (27.81%) had partial remission, and 43 patients (31.85%) relapsed. The level of serum sIL-2R at the AL initial diagnosis period was (533±32) U/ml, which was higher than that in the healthy controls [(247±30) U/ml], and the difference was statistically significant ( t = 71.976, P < 0.01); the level of serum SDF-1α at the AL initial diagnosis was (2 968±305) pg/ml, which was higher than that in the healthy controls [(1 358±160) pg/ml], and the difference was statistically significant ( t = 47.043, P < 0.01). The levels of serum sIL-2R [(308±30) U/ml] and SDF-1α [(1 576±184) pg/ml] in the CR phase were lower than those in the initial diagnosis of patients with AL; and the levels of sIL-2R [(599±36) U/ml] and SDF-1α [(2 894±301) pg/ml] in the relapse phase were higher than those in the CR phase of patients with AL (all P < 0.01). Conclusions:The levels of serum sIL-2R and SDF-1α in patients with AL are increased, and there are big differences in the levels of sIL-2R and SDF-1α at the initial diagnosis, remission phase, and relapse phase. Dynamic monitoring of both can provide the data support for early clinical intervention.

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.

Objective: To investigate the clinical characteristics, cell morphology, genetics, gene mutations of the patients with chronic neutrophilic leukemia (CNL). Methods: Five CNL patients from the Second Hospital of Shanxi Medical University between May 2011 and May 2017 who conformed to 2016 World Health Organization (WHO) diagnostic criteria were retrospectively analyzed from clinical characteristics, laboratory features and treatment methods. Results: The peripheral blood white blood cell count (WBC) of 5 CNL patients was significantly increased, and the average WBC was 81.26×10⁹/L [(29-217)×10⁹/L]. Morphological analysis of peripheral blood cell showed a sustained increasing number of matured neutrophilia (0.80-0.85). Neutrophil alkaline phosphatase (NAP) activity was increased (144-266). Bone marrow cell morphology typically showed granulocyte proliferation without obvious dysplasia. Gene detection showed 3 patients with CSF3R T618I mutation and 2 patients with JAK2 V617F mutation in 5 WHO-defined CNL patients. Bone marrow biopsy with reticular staining showed that marrow fibrosis (MF) degree in patients with JAK2 V617F mutation (MF≥2) was higher than that in patients with CSF3R T618I mutation(MF<2). Conclusions CNL is a rare type of chronic leukemia, and CSF3R T618I mutation is a specific diagnostic index for CNL. JAK2 V617F mutations alone may be related to myelofibrosis, which remains to be further studied.

Objects:To investigate the current situation of counselors'implementation and their attitude to informed consent in Beijing.Methods:Eleven counselors who worked in Beijing were interviewed,the average of their working years was (7.4 ± 4.4).A semi-structured interview was used to learn about their practicing processes in and viewpoints on informed consent,and their interview transcripts were analyzed through qualitative method.Results:The results could be categorized into four categories,including the content of informed consent,the influential factors of informed consent,problems and confusions,and the significance of informed consent.The crucial role of informed consent in psychotherapy was generally recognized by counselors,and they could obey the related rules as well.The therapists had some confusion and problems about informed consent,such as the form and length,the consent for special population and online consultation.Conclusion:Basically,the counselors in Beijing could comply with the ethical standards of informed consent.However,they also suggest that certain limitations of these rules should be noticed.

In recent years , there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+LPD), and the name of EBV +LPD is used widely.However,the meaning of EBV+LPD used is not the same , which triggered confusion of the understanding and obstacles of the communication.In order to solve this problem.Literature was reviewed with combination of our cases to clarify the concept of EBV +LPD and to expound our understanding about it .In general, it is currently accepted that EBV +LPD refers to a spectrum of lymphoid tissue diseases with EBV infection , including hyperplasia , borderline lesions , and neoplastic diseases .According to this concept , EBV+LPD should not include infectious mononucleosis ( IM ) and severe acute EBV infection ( EBV +hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+lymphomas ( such as extranodal NK/T cell lymphoma , aggressive NK cell leukemia , Burkitt lymphoma, and Hodgkin lymphoma , etc.) either.EBV +LPD should currently include: ( 1 ) EBV +B cell-LPD:lymphomatoid granulomatosis , EBV +immunodeficiency related LPD , chronic active EBV infection-B cell type, senile EBV +LPD, etc.(2) EBV +T/NK cell-LPD:CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc.In addition, EBV+LPD is classified, based on the disease process , pathological and molecular data , as 3 grades:grade1, hyperplasia ( polymorphic lesions with polyclonal cells ); grade 2, borderline ( polymorphic lesions with clonality ); grade 3, neoplasm (monomorphic lesions with clonality).There are overlaps between EBV +LPD and typical hyperplasia, as well as EBV+LPD and typical lymphomas .However , the most important tasks are clinical vigilance , early identification of potential severe complications , and treating the patients in a timely manner to avoid serious complications , as well as the active treatment to save lives when the complications happened .