AIM:To investigate the effects of modified Danggui Yinzi decoction combined with diclofenac sodium eye drops on tear film stability and tear protein levels in patients with allergic conjunctivitis.METHODS:Prospective study. Patients with allergic conjunctivitis who attended Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from March 2021 to August 2024 were enrolled as study subjects. They were divided into two groups based on their treatment regimen: a control group(treated with diclofenac sodium eye drops alone)and an observation group(treated with modified Danggui Yinzi decoction combined with diclofenac sodium eye drops). Propensity score matching was used to balance baseline characteristics between the two groups. Log-binomial regression was performed to estimate the risk of adverse reactions. Repeated-measures analysis of variance(ANOVA)was used to assess tear film stability indicators. A difference-in-differences(DID)model was employed to assess the net effect of the combined therapy on changes in tear protein levels.RESULTS:After propensity score matching, a total of 172 patients(344 eyes)were finally enrolled, with 86 patients(172 eyes)in each of the control and observation groups. In the control group, there were 51 males and 35 females, with a mean age of 35.91±10.10 y; in the observation group, there were 49 males and 37 females, with a mean age of 37.87±8.09 y. After treatment, symptom scores decreased in both groups compared with baseline(all P<0.05). At 2 and 4 wk after treatment, symptom scores in the observation group were significantly lower than those in the control group(all P<0.05). The overall response rate was significantly higher in the observation group(89.5%)than in the control group(77.9%)(P<0.05), while the incidence of total adverse reactions was significantly lower in the observation group(7.0%)than in the control group(36.0%)(RR=0.133, P<0.001). Compared with baseline, both groups showed increases in BUT and SⅠt, and a decrease in FL score at 2 and 4 wk after treatment(P<0.017). At 2 and 4 wk after treatment, the BUT and SⅠt levels in the observation group were higher than those in the control group, and the FL score was significantly lower(all P<0.05). The DID model showed that the observation group had greater increases than the control group in lactoferrin(0.411 g/L), total protein(2.792 g/L), secretory immunoglobulin A(14.610 mg/L), and lysozyme(0.419 g/L), respectively(all P<0.05), and these differences remained significant after adjusting for covariates.CONCLUSION:Modified Danggui Yinzi decoction combined with diclofenac sodium eye drops significantly improves tear film stability indicators and tear protein levels in patients with allergic conjunctivitis, and its therapeutic efficacy is superior to that of diclofenac sodium eye drops alone.

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.

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

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.

Objective:This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures.Methods:This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection.Results:The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P<0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P<0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P<0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR=1.479, 95% CI 1.169-1.872, P=0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR=0.584, 95% CI 0.421-0.820, P=0.002), the >50-year age group ( OR=0.389, 95% CI 0.248-0.610, P<0.001) ], and the lifting of COVID-19 restrictions ( OR=2.360, 95% CI 1.287-3.047, P<0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR=1.499, 95% CI 1.138 - 1.975, P=0.004) and the lifting of COVID-19 restrictions ( OR=2.608, 95% CI 1.940-3.507, P<0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR=2.222, 95% CI 1.101-4.484, P=0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions:Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

Objective:This study aimed to analyze the clinical manifestations of human herpesvirus 6 (HHV-6) infection within 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to investigate the association of HHV-6 viral load with clinical outcomes as well as the effect of antiviral treatment on the course of HHV-6 infection.Methods:This retrospective study included patients who tested positive for HHV-6 within 100 days after allo-HSCT at the Peking University Institute of Hematology from February 2016 to February 2023. The study analyzed the patients' baseline characteristics, including age and transplantation type, as well as their clinical manifestations. Additionally, post-transplant complications were examined.Results:This study detected that 305 patients with HHV-6 infection were positive with a median time of 20 days post-transplant. Fifteen patients were asymptomatic, whereas the remaining patients exhibited the following symptoms: fever, rash, diarrhea, hemorrhagic cystitis, delayed platelet engraftment, central nervous system symptoms, abdominal pain, pneumonia and perioral numbness. Acute graft-versus-host disease (aGVHD) was diagnosed in 189 patients, with 45 cases of HHV-6 infection occurring before the onset of aGVHD and 120 cases occurring after aGVHD developed. Quantitative HHV-6 detection was available for 45 patients, and no statistically significant differences were found in the clinical manifestations according to the viral titer. A total of 108 (35.41%) patients experienced coactivation with other viruses, including cytomegalovirus, BK virus, and Epstein-Barr virus (EBV). Notably, coinfection with EBV was determined as an independent risk factor for overall survival (OS). No statistically significant difference in the time to HHV-6 viral clearance was observed between the antiviral treatment and non-treatment groups [7 (5-10) days vs 8 (4-14) days, P=0.199]. Similarly, the 5-year OS rates between the two groups were not significantly different [ (82.7 ± 2.6) % vs (91.3 ± 3.1) %, χ2=3.304, P=0.069]. Discussion:The most prevalent clinical manifestations were fever, rash, and diarrhea in patients with HHV-6 infection after allo-HSCT. No significant correlation was found between the severity of the clinical symptoms and the viral titer. Additionally, no significant differences in the time to HHV-6 clearance or 5-year OS were observed between patients who received antiviral treatment and those who did not.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease