ObjectiveTo explore the potential mechanism of Weicanqing Formula （微残清方， WF） combined with chemotherapy in treating acute myeloid leukemia （AML） based on malic enzyme 2 （ME2）-mediated bone marrow immune-metabolic homeostasis and . MethodsSixty-five male C57BL/6N mice were randomly divided into control group， model group， WF group， chemotherapy group， and the combination group （WF plus chemotherapy）， with 13 mice per group. Except for the control group， mice were injected with C1498 cells （appro-ximately 1×10⁶ cells per mouse） via the tail vein on day 1 to establish an AML model. Starting from day 8， mice in the chemotherapy group and the combination group were administered with cytarabine at 30 mg/（kg·d） via subcutaneous injection， once daily for 3 consecutive days； WF group and the combination group received WF at 7.54 g/（kg·d） by gavage， once daily for 21 consecutive days. On days 1， 7， 14， 21 and 28， hemoglobin （Hb） and white blood cell （WBC） levels were determined in each group. On day 28， Giemsa staining was used to observe morphological changes in bone marrow cells. Flow cytometry was employed to detect the expression levels of bone marrow T lympthocyte subsets， including CD8⁺， CD4⁺， and regulatory T lymphocytes （Treg）. The contents of glutamine （Gln）， nicotinamide adenine dinucleotide phosphate （NADP⁺）， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in bone marrow were determined using visible spectrophotometry. Adenosine triphosphate （ATP） concentration in bone marrow was measured by chemiluminescence assay. The mRNA expression of malic enzyme 2 （ME2） in bone marrow was detected by RT-qPCR， and the protein expression level of ME2 was determined by Western blotting. ResultsCompared to the control group， the model group showed decreased Hb levels on day 14， 21， and 28， and increased WBC levels on day 7， 14， 21， and 28 （P＜0.05）. On day 28， bone marrow CD8⁺ and CD8⁺/CD4⁺ levels decreased， while Treg cells， ATP， Gln， NADP⁺， NADPH， ME2 mRNA， and their corresponding protein levels increased （P＜0.05）. Compared to the model group， the chemotherapy group and the combination group both exhibited reduced Hb level on day 14， 21 and 28， as well as the increased WBC level； the combination group showed increased CD8⁺ level， decreased Treg， ATP， Gln， and NADPH content， as well as reduced ME2 mRNA expression and protein levels （P＜0.05）. Compared to the chemotherapy group， the combination group showed significantly increased Hb level on days 21 and 28， and increased WBC level on day 28 （P＜0.05）. Bone marrow smear pathology revealed that， in the model group， myeloid blast cells exhibited cytoplasmic vacuoles indicative of abnormal metabolic activity. In contrast， both the chemotherapy group and the combination group showed large numbers of metamyelocytes and band neutrophils， with only a few immature granulocytic blast cells observed. ConclusionWF may improve the prognosis of AML when used as an adjunct to chemotherapy by modulating ME2 expression， inhibiting metabolic energy competition within the bone marrow microenvironment， and reshaping the distribution of T lymphocyte subsets in the bone marrow.

Objective:To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA).Methods:A male patient presented with primary infertility for 1 year post-marriage, intellectual disability, and blepharoptosis at Huzhou Maternity and Child Health Care Hospital from October to December 2024 was selected as the study subject. Peripheral blood samples were collected from the patient and his family members. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Ethics Committee of the Huzhou Maternity and Child Health Care Hospital (Ethics No. 2023-R-010).Results:The patient, a 29-year-old male, had exhibited short stature, trigonocephaly, bilateral blepharoptosis, arched eyebrows, brachydactyly, redundant skin folds, webbed neck, hypertrichosis, mild intellectual disability, and speech impairment. WES revealed that he has harbored a de novo heterozygous frameshifting variant of the ZNF462 gene, namely c. 945_946del (p.T316Rfs*42). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM2_Supporting+ PVS1+ PM6_Supporting). Conclusion:The ZNF462 c. 945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA). METHODS: A male patient presented with primary infertility for 1 year post-marriage, intellectual disability, and blepharoptosis at Huzhou Maternity and Child Health Care Hospital from October to December 2024 was selected as the study subject. Peripheral blood samples were collected from the patient and his family members. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Ethics Committee of the Hospital (Ethics No. 2023-R-010). RESULTS: The patient, a 29-year-old male, had exhibited short stature, trigonocephaly, bilateral blepharoptosis, arched eyebrows, brachydactyly, redundant skin folds, webbed neck, hypertrichosis, mild intellectual disability, and speech impairment. WES revealed that he has harbored a de novo heterozygous frameshifting variant of the ZNF462 gene, namely c.945_946del (p.T316Rfs*42). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM2_Supporting+PVS1+PM6_Supporting). CONCLUSION The ZNF462 c.945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.
Humans ; Male ; Adult ; Intellectual Disability/genetics* ; Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Abnormalities, Multiple/genetics* ; Blepharoptosis/genetics*

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

Objective:To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA).Methods:A male patient presented with primary infertility for 1 year post-marriage, intellectual disability, and blepharoptosis at Huzhou Maternity and Child Health Care Hospital from October to December 2024 was selected as the study subject. Peripheral blood samples were collected from the patient and his family members. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Ethics Committee of the Huzhou Maternity and Child Health Care Hospital (Ethics No. 2023-R-010).Results:The patient, a 29-year-old male, had exhibited short stature, trigonocephaly, bilateral blepharoptosis, arched eyebrows, brachydactyly, redundant skin folds, webbed neck, hypertrichosis, mild intellectual disability, and speech impairment. WES revealed that he has harbored a de novo heterozygous frameshifting variant of the ZNF462 gene, namely c. 945_946del (p.T316Rfs*42). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM2_Supporting+ PVS1+ PM6_Supporting). Conclusion:The ZNF462 c. 945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.

Domestic and foreign literatures related to the persistence of SARS-CoV-2 and the re-positive cases infected with SARS-CoV-2 were reviewed, and the characteristics and infectivity of the re-positive cases were analyzed to provide scientific evidence for the improvement of case management and the development of measures to stop the spread of SARS-CoV-2. Existing studies have shown that re-positive rate of SARS-CoV-2 ranged from 2.4% to 19.8%, the median of interval between re-positive detection and discharge was 4-15 days. Following the second course of the disease, the anti-SARS-CoV-2 IgM, IgG and IgA positive rates of the cases were 11.11%-86.08%, 52.00%-100.00% and 61.54%-100.00% respectively, the total antibody and neutralizing antibody positive rates were 98.72% and 88.46%. The viral load of the re-positive cases was lower than that in the initial infection. At least 3 380 re-positive cases have been reported globally. SARS-CoV-2 strains were isolated from the samples of 3 re-positive cases (1 immunodeficiency case and 2 cases with abnormal pulmonary imaging). There were close contacts that were infected by an asymptomatic case taking immunosuppressive agents. In conclusion, the infectivity of re-positive cases infected with SARS-CoV-2 is generally very low. Rare re-positive cases infected with SARS-CoV-2 might cause further transmission. The management approach for the re-positive cases can be based on the assessment of the individual transmission risk according to the pathogen detection results.
Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin M ; SARS-CoV-2

Objective:To explore the annexin A2 (ANXA2) expression and distribution in dorsal root ganglion (DRG) after chronic compression of DRG (CCD) in rat models.Methods:One hundred and two adult male Wistar rats were randomly divided into control group ( n=24), CCD model group A (7 d after modeling, n=30), CCD model group B (14 d after modeling, n=24), and CCD model group D (28 d after modeling, n=24). Rats in the later 3 groups were established CCD models with the help of "U" rod screw. Mechanical withdrawal threshold (MWT) and thermal radiation paw withdrawal latency (TWL) were measured by mechanical pain stimulator and thermal pain stimulator. The ANXA2 protein expression in the DRG was detected by Western blotting and immunofluorescent staining. The distributions of ANXA2 and class III β-tubulin (TUBB3) positive cells in DRG were detected by immunofluorescence double staining. Results:As compared with those in the control group, MWT and TWL in the CCD model group A and CCD model group B were significantly decreased ( P<0.05). Western blotting showed that ANXA2 protein expression in the DRG of CCD model group A was statistically increased as compared with that in the control group ( P<0.05). Immunofluorescent staining showed that the immunoreactivity of ANXA2 in DRG of CCD model group A was enhanced as compared with that in control group. Immunofluorescence double staining showed that ANXA2 was mainly expressed in the cell membrane of neurons in the DRG of CCD model group A. Conclusion:The mechanical and thermal pain thresholds are decreased, while the ANXA2 protein expression at the pressure side of DRG is up-regulated and the immunoreactivity is increased in CCD models; ANXA2 may be involved in the occurrence and development of pathological neuralgia after CCD.

Objective To quantify the risk factors for aspirin resistance so as to increase the prognosis for risk of coronary heart disease,and to establish a predictive model for aspirin resistance in order to guide the clinical anti-platelet therapy.Methods A total of 938 elderly male patients with stable coronary heart disease (CHD) receiving oral aspirin therapy (＞75 mg/d) over 2 months were included in this study.Their clinical data were collected.Logistic regression analysis was performed to establish a predictive model and risk score for aspirin resistance.Hosmer Lemeshow (H-L) test and an area under the receiver operating characteristic (ROC) curve (the area under the ROC curve) were performed to test the calibration and discrimination of the model.Results Seven risk factors were included in the predictive model,including serum creatinine (＞110 μmol/L:score of 1),fasting blood glucose (＞7.0 mmol/L:score of 1),hyperlipidemia (score of 1),number of coronary arteries in lesion (2 branches:score of 2,≥≥3 branches:score of 4),body mass index[(20-25) kg/m2:score of 2,＞25 kg/m2:score of 4],percutaneous coronary intervention (score of 2),smoking (score of 3).H-L test showed P≥0.05 and the area under the ROC curve＞0.70 in this model.Conclusions the risk factors for aspirin resistance,and establishing a valid predictive model for aspirin resistance,could provide an important reference for anti-platelet therapy in CHD patients.