BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Objective:To evaluate the safety and efficacy of donor-purified CD34 + stem cell boosts in patients with poor hematopoietic reconstruction (PHR) after haploid hematopoietic stem cell transplantation (haplo-HSCT) for aplastic anemia (AA) . Method:A retrospective analysis was conducted on 11 patients with AA and PHR who underwent haplo-HSCT and received donor-purified CD34 + stem cell boosts at Peking University People’s Hospital. Recovery of blood cell counts, incidence of graft-versus-host disease (GVHD), and overall survival (OS) were assessed. Results:Of the 11 patients with PHR, two were diagnosed with prolonged isolated thrombocytopenia (PT), one was primary poor graft function (PGF), and eight were diagnosed with secondary PGF. The median time to PHR diagnosis was 110 days (range: 60-330 days), and the median interval from transplantation to purified CD34 + hematopoietic stem cell infusion was 194 days (range: 125-456 days). The two patients with PT achieved complete platelet recovery at 22 and 13 days after CD34 + stem cell infusion, respectively. Among the remaining nine patients with PGF, six achieved complete hematopoietic recovery, with a median absolute neutrophil count recovery time of 19 days (8-158 days), HGB recovery time of 32.5 days (range: 13-158 days), and platelet recovery time of 31.5 days (range: 7-171 days). The incidence of chronic GVHD after infusion was 18.2%, with no cases of acute GVHD observed. The OS rate was 90.9% (10/11) in the 11 patients, with a median follow-up of 614 days (range: 153-1 765 days) . Conclusion:Donor-purified CD34 + stem cell boost may be an effective therapeutic strategy for PHR in patients with AA after haplo-HSCT.

BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Objective:To evaluate the safety and efficacy of donor-purified CD34 + stem cell boosts in patients with poor hematopoietic reconstruction (PHR) after haploid hematopoietic stem cell transplantation (haplo-HSCT) for aplastic anemia (AA) . Method:A retrospective analysis was conducted on 11 patients with AA and PHR who underwent haplo-HSCT and received donor-purified CD34 + stem cell boosts at Peking University People’s Hospital. Recovery of blood cell counts, incidence of graft-versus-host disease (GVHD), and overall survival (OS) were assessed. Results:Of the 11 patients with PHR, two were diagnosed with prolonged isolated thrombocytopenia (PT), one was primary poor graft function (PGF), and eight were diagnosed with secondary PGF. The median time to PHR diagnosis was 110 days (range: 60-330 days), and the median interval from transplantation to purified CD34 + hematopoietic stem cell infusion was 194 days (range: 125-456 days). The two patients with PT achieved complete platelet recovery at 22 and 13 days after CD34 + stem cell infusion, respectively. Among the remaining nine patients with PGF, six achieved complete hematopoietic recovery, with a median absolute neutrophil count recovery time of 19 days (8-158 days), HGB recovery time of 32.5 days (range: 13-158 days), and platelet recovery time of 31.5 days (range: 7-171 days). The incidence of chronic GVHD after infusion was 18.2%, with no cases of acute GVHD observed. The OS rate was 90.9% (10/11) in the 11 patients, with a median follow-up of 614 days (range: 153-1 765 days) . Conclusion:Donor-purified CD34 + stem cell boost may be an effective therapeutic strategy for PHR in patients with AA after haplo-HSCT.

Hepatosplenic candidiasis (HSC) is a rare type of candidiasis that can occur in patients with hematologic malignancies, hematopoietic stem cell transplantation. At present, there is still a lack of studies on HSC in patients with hematologic disorders. Based on The Chinese Guidelines for the Diagnosis and Treatment of Invasive Fungal Disease in Patients with Hematological Disorders and Cancers (the 6th revision), We retrospectively analyzed the clinical characteristics and prognosis of patients with HSC treated in Peking University Institute of Hematology from 2008 to 2022. Finally, eighteen patients were included, with 1 (5.6%) proven, 2 (11.1%) probable, and 15 (83.3%) possible HSC. Among them, 3 (16.7%) patients occurred after haploid hematopoietic stem cell transplantation and 15 (83.3%) patients occurred after chemotherapy. 6 (33.3%) patients had positive blood cultures, including 4 cases of Candida tropicalis and 2 cases of Candida albicans. At 4 weeks of antifungal therapy, 10 (58.8%) patients achieved partial response (PR), At 8 weeks, 1 (6.3%) patients achieved complete response and 10 (62.5%) patients achieved PR. At 6 months after diagnosis, 3 (16.7%) patients died of hematopoietic recurrence, and none of them died of HSC. As a rare fungal infection disease, HSC has a low positive rate of microbiological and histological examinations, a persistent treat cycle, and has difficulty in remission, reminding us of the need for vigilance in patients with hematopoietic disorders and persistent fever.