To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

ObjectiveTo investigate the status and influencing factors of latent tuberculosis infection (LTBI) among close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, and to provide scientific evidence for the development of tuberculosis infection testing and preventive intervention strategies for close contacts of bacteriologically positive patients. MethodsFrom October 2022 to October 2023, patients with bacteriological confirmed pulmonary tuberculosis registered in Jing’an District, Shanghai, and their close contacts were enrolled as the research subjects. The close contacts were screened for tuberculosis infection using the interferon-γ release assay (IGRA). The chi-square test and binary logistic regression model were used to analyze factors influencing LTBI. ResultsA total of 112 close contacts were included, of whom 30 (26.79%) were male and 82 (73.21%) were female. The age ranged from 1 to 86 years, with a median (25th, 75th percentiles) of 47.50 (32.25, 61.00) years. The infection rate of LTBI was 21.43% (24/112), and the incidence of active pulmonary tuberculosis was 2.68% (3/112). Univariate analyses showed that a positive sputum smear of the index case, being a direct relative of the index case, co-living, and not wearing a mask were significantly associated with LTBI (all P<0.05). Multivariate logistic regression analyses showed that the risk of latent infection in close contacts of the index case with a positive sputum smear was 6.50 times higher than in those with a negative sputum smear (95%CI: 1.82‒23.25, P=0.004). ConclusionThe infection rate of LTBI in close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, is relatively high, and close contacts of sputum smear-positive patients face an even higher risk of infection. Therefore, tuberculosis infection screening and follow-up management should be strengthened for this population.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To report the clinical, imaging, and pathological features of a case of MYH7 gene-related scapuloperoneal myosin storage myopathy. Methods:Clinical data were collected from a patient with MYH7 gene-related scapuloperoneal myosin storage myopathy who presented to Peking University First Hospital in February 2025. The patient was evaluated with muscle magnetic resonance imaging, muscle biopsy, and whole-exome sequencing. Results:The patient was a 52-year-old female, with a 12-year history of progressive difficulty in foot dorsiflexion, exercise-induced fatigue, and lower limb pain. Over the past 3 years, she developed proximal upper limb weakness and post-exertional myalgia. Physical examination revealed scapuloperoneal weakness distribution accompanied by sensorineural hearing loss. Electromyography demonstrated myogenic changes in the deltoid and tibialis anterior muscles. Serum creatine kinase levels were within normal limits. Lower limb magnetic resonance imaging showed mild atrophy of the thigh muscles and significant fatty infiltration in the tibialis anterior, extensor hallucis longus, and extensor digitorum longus. Tibialis anterior muscle biopsy revealed dystrophic-like changes with sub-sarcolemmal hyaline bodies containing abundant granulofilamentous material. Whole exome sequencing identified a heterozygous pathogenic variant of c.5352_5354del(p.K1784del) in the MYH7 gene. Conclusions:This patient is the first reported one in China with MYH7 gene-related scapuloperoneal myosin storage myopathy, exhibiting characteristic scapuloperoneal weakness, selective fatty infiltration of the anterior lower leg muscles on imaging and sub-sarcolemmal hyaline body pathological changes. The diagnosis of this disease relies on characteristic pathological findings and genetic test results.

Objective:To explore the application value of the artificial intelligence (AI) morphological assisted analysis system in the pre-classification of blood cells in patients with acute myeloid leukemia, myelodysplasia-related (AML-MR).Methods:A retrospective analysis was conducted on the bone marrow and peripheral blood cell morphology of patients initially diagnosed with AML-MR at Taizhou Hospital in Zhejiang Province from September 1, 2022, to December 31, 2023. A total of 44 patients, including 25 males and 19 females, with a median age of 71 (63.5, 75.3) years. Bone marrow and peripheral blood morphology were examined using the Morphogo cell morphology assisted analysis system, with the artificial classification results serving as the gold standard. A confusion matrix was constructed to evaluate the precision, sensitivity, and specificity of the AI system in identifying various cell types in bone marrow and peripheral blood for AML-MR diagnosis. The impact of dysplastic hematopoiesis on AI pre-classification was analyzed by comparing AI and manual classification results.Results:The AI system completed the pre-classification of 44 bone marrow smears and 42 corresponding peripheral blood smears from AML-MR patients. For bone marrow smears, the precision, sensitivity, and specificity of AI in pre-classifying blast cells were 85.78%, 91.01%, and 94.58%, respectively. For peripheral blood smears, these values were 87.11%, 87.05%, and 98.29%, respectively. The precision and sensitivity of AI in pre-classifying promyelocytes were 54.26% and 46.93%, respectively, while for monocytes, they were 58.16% and 68.34%, both lower than those for blast cells. The precision and sensitivity of AI in identifying myelocytes and metamyelocytes also decreased (77.47%, 66.25% and 81.91%, 63.29%, respectively). The precision and sensitivity of AI in pre-classifying erythroblasts/proerythroblasts (67.71%, 69.89%) were lower than those for polychromatic and orthochromatic normoblasts (83.43%, 85.53% and 92.97%, 86.96%, respectively). The confusion matrix and comparative analysis of AI and manual classification indicated that the decline in AI pre-classification precision and sensitivity was due to frequent misclassification between promonocytes and monocytes, as well as between monocytes and promyelocytes. Additionally, this decline is associated with dysplasia. However, the impact of dysplasia on the AI pre-classification of mature-stage granulocytes was minimal.Conclusion:The AI system demonstrated high precision, sensitivity, and specificity in pre-classifying blast cells in bone marrow and peripheral blood smears from AML-MR patients. The AI-assisted morphological analysis system can be effectively utilized for the pre-classification of blood cells in AML-MR patients.

Objective:To explore the immunophenotypic differences between acute promyelocytic leukemia (APL) and APL-like NPM1 mutant acute myeloid leukemia (NPM1mutAML) using flow cytometry, and to investigate early diagnostic markers for differentiating APL from NPM1mutAML.Methods:A retrospective study was conducted on 72 cases of APL diagnosed at Taizhou Hospital, affiliated with Wenzhou Medical University, from February 2nd, 2018 to December 16th, 2023, including 42 male and 30 female patients with a median age of 42 (32, 57) years old. Based on morphology, 51 cases were classified as the coarse-granular type and 21 cases as the fine-granular type. Additionally, 45 cases of NPM1mutAML, comprising 20 male and 25 female patients with a median age of 58 (47, 65) years old, were included. Of these, 12 cases were classified as the coarse-granular type and 33 as the fine-granular type. Immunophenotypic analysis was performed using multiparameter flow cytometry, and all patients underwent cytogenetic analysis for chromosome karyotyping. FISH analysis was used for detecting the PML-RARα fusion gene in APL cases, and sequencing was used for identifying NPM1 mutations in NPM1mutAML patients. The antigen expression parameters (expression rate, median fluorescence intensity [MdFI], and coefficient of variation [ CV]) were analyzed using principal component analysis (PCA). The antigen expression rates were compared using the Wilcoxon rank-sum test, and the positive rates of antigens were compared using the Chi-square test. Sensitivity and specificity for diagnosis by the some antigens were evaluated using ROC curve analysis. Results:The immunophenotypic analysis revealed that the expression rates of CD123, CD64, CD13, and CD9 were significantly higher in APL compared to NPM1mutAML ( Z values of-6.72, -6.29, -5.63, -7.67, P<0.01). In the coarse-granular type, the expression rates of CD123 and CD9 in APL were also significantly higher than those in NPM1mutAML ( P<0.01). In the fine-granular type, the expression levels of CD123, CD13, CD64, and CD9 were significantly higher in APL than in NPM1mutAML ( P<0.01). ROC curve analysis showed that in the fine-granular type, the areas under the curve (AUC) for CD64, CD13, CD123, and CD9 in diagnosing APL and NPM1mutAML were 0.96, 0.89, 0.86, and 0.89, respectively ( P<0.01). In the coarse-granular type, the AUC for CD64 and CD13 were 0.49 and 0.51 ( P>0.05), while the AUC for CD123 and CD9 were 0.96 and 0.96 ( P<0.01). Principal component analysis (PCA) of antigen expression (expression rate, MdFI, CV) showed complete separation of the APL and NPM1mutAML groups. Conclusion:APL and APL-like NPM1mutAML patients exhibit distinct antigen expression profiles. Specifically, a combined detection of CD64, CD13, CD123, and CD9 can help to rapidly differentiate APL from APL-like NPM1mutAML at initial diagnosis.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To examine the effect of antidepressant treatment on the longitudinal depressive burden in patients with bipolar depression.Methods:Subjects were recruited from a national multicenter, naturalistic observational project: Comprehensive Assessment and Follow-up Descriptive Study on Bipolar Disorder study (CAFE-BD). A total of 110 patients with bipolar depression (51 males, 59 females; aged 18-64 years, mean age 34.4±11.1 years) were consecutively enrolled between January 2012 and December 2013 from outpatients and inpatients of nine medical institutions, including six psychiatric hospitals and three general hospitals. Based on the use of antidepressants as defined in this study, patients were classified into a medicated group (Ads, n=74) and a non-medicated group (nAds, n=36). Diagnosis of bipolar depression was confirmed using the MINI (Chinese version), and baseline and follow-up assessments were conducted using the Assessment of Mood Disorders Evaluation (ADE) and the Clinical Monitoring Form (CMF). Depression burden indicators, including aggregate depression scores (SUM-D), number of depressive symptoms (NUM-D), and total depression burden, were compared between the Ads group and nAds group at mid-term (the 6 th month) and endpoint (the 12 nd month). Longitudinal changes in these indicators were also analyzed. Results:The proportion of bipolar depressive patients on antidepressants was 67% (74/110). Among them, 85% (63/74) were taking antidepressants at baseline; this dropped to 76% (56/74) at mid-term, and 64% (47/74) at the endpoint. SUM-D were higher in the Ads group than in the nAds group at baseline (9 (6.5, 11) vs 7.38 (5.5, 9.0); W=1 712.00, P=0.015), and there was no statistically significant difference in NUM-D and total depressive burden between two groups at any time points ( P>0.05). Compared to baseline, the Ads group had significantly lower SUM-D (0.5 (0, 1), 1.33 (0.5, 2.5) vs. 9 (6.5, 11); W=2 770.00, 2 743.00), NUM-D (0 (0, 0), 0 (0, 1) vs. 7 (5, 8); W=2 621.00, 2 601.50) and total depressive burden (c 2=64.36, 59.00) at both mid-term and endpoint (all P<0.001); While SUM-D (0.59 (0.4, 0.7), 1 (0.8, 2.5) vs. 7.38 (5.5, 9.0); W=664.50, W=666.00), NUM-D (0 (0, 0), 0 (0, 1) vs. 6 (4, 7); W=527.00, 528.00) and total depression burden ( χ 2=31.00, 31.00) in the nAds group were also significantly decreased at both mid-term and endpoint (all P<0.001). There were no statistically significant differences in the changes in depression burden indicators between the two groups from baseline to mid-follow-up or endpoint, nor from mid-follow-up to endpoint ( P>0.05). Conclusion:In a 12-month real-world naturalistic follow-up study, both medicated and non-medicated bipolar depression groups experienced significant and similar reductions in depression burden.