Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

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.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Objective: To analyze the clinical value of real-time PCR for virus detection in the diagnosis and treatment of patients after allo-HSCT who had no infection evidence of pneumonia using routine pathogen detection panel. Methods: The clinical data of 71 episodes with acute lung injury from May 2015 to March 2017 after allo-HSCT in hematology department of Peking University People’s Hospital (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF) samples. Results: Among 71 episodes with acute lung injury, a total of 15 patients were diagnosed as lower respiratory tract disease merely associated with virus (detection rate of 21.13%) , 19 episodes were absent of lower respiratory tract infection. The median time from allo-HSCT to the occurrence of lung injury were 176 (49-1 376) d and 196 (57-457) d respectively (z=-0.191, P=0.864) . There were no statistical differences for baseline characteristics and clinical features between two groups. The 100-day attributable mortalities were 13.3% (2/15) and 26.3% (5/19) (χ²=0.864, P=0.426) . Patients with low-dose steroids treatment had favorable outcome than those with high-dose steroids treatment (the dose of methylprednisolone ≥250 mg/d as standard) [4.2% (1/24) vs 60.0% (6/10) ]. In patients with detectable virus in BALF, 2 patients died with early high-dose steroids treatment, while 11 patients survived with no steroids treatment or late application. Conclusions Virus infection should be considered in post-HSCT pneumonia patient with negative result using routine pathogen detection panel. Expanding virus detection panel by PCR in BALF could increase diagnostic precision and might be instructive to treatment.

Chronic constipation was a common gastrointestinal disease, which was characterized by decreased defecation,decreased amount of feces, dry feces and exertion in defecation. The incidence of chronic constipation was high with a tendency of increasing by year. The elderly people were high risk population of chronic constipation. Chronic constipation not only resulted in anal diseases including hemorrhoid and anal fissure, but also induced or exacerbates cardiovascular and cerebrovascular diseases, even could induce colon cancer which affected the life of quality of old people. It also caused high health care costs and increased the economic burden of patients and society. The study reviewed the epidemiology and influencing factors of elderly people chronic constipation through the collection, analysis and conclusion of recent references.

Objective To evaluate the immunoprotection by the inactivated whole bacteria(IWB) of Stenotrophomonas maltophilia K279a in mice.Methods Mice were immunized by inactivated whole bacteria of S.maltophilia K279a made from formaldehyde.When the indicated the antibody titer of the mice reached the require level, the protective effect of the IWB was evaluated by performing the opsonophagocytic killing test in vitro and the poison attack experiments in vivo. Results It was found that IgG in serum of the immunized mice measured by ELISA was significantly increased after the second immune enhancement, and antiserum in vitro had strong phagocytic effect.Meanwhile, immunoprotection of the immunized groups was also significantly increased when challenged by S.maltophilia K279a.Conclusion Effective humoral immune response can be predominantly induced by the inactivated whole bacteria of S.maltophilia K279a, providing protection against challenge by S.maltophilia K279a in BALB/c mice.