Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

The dried mature peel of Citrus reticulata, a plant in the Rutaceae family and its cultivated varieties, is a commonly used Chinese medicinal material known as Chenpi(Citri Reticulatae Pericarpium). It is rich in nutritional components and medicinal value, with pharmacological effects including relieving cough and eliminating phlegm, strengthening the spleen and drying dampness, protecting the liver and benefiting the stomach, tonifying Qi, and calming the mind. Huanglongbing(HLB), also known as Citrus Huanglongbing, is a destructive disease in citrus production that seriously threatens the development of the citrus industry. HLB causes symptoms such as the inability of Rutaceae plants to produce mature fruit, gradual weakening of the tree, and eventual death, posing a significant threat to the yield and quality of Chenpi. Due to the uneven distribution of the HLB pathogen in infected plants, accurate detection of the pathogen requires the collection of a large number of plant samples. Current sample pretreatment methods, such as traditional extraction methods and commercial extraction kits, are time-consuming and involve multiple steps, which significantly increase the difficulty and workload of HLB diagnosis and have become a bottleneck in HLB detection. In this study, a rapid high-throughput detection method combining alkali lysis and TaqMan qPCR was developed. This method allows the pretreatment of multiple samples within 5 min, and the entire detection process can be completed within 45 min, with a detection limit of 6.67 fg·μL~(-1). The alkali lysis method and commercial kits were used for parallel detection of field-collected citrus samples, and the results showed no significant difference. The sample pretreatment method established in this study is characterized by low cost, simplicity, and high efficiency. Combined with TaqMan qPCR, it can provide technical support for early and on-site diagnosis of HLB. This method is of great significance for disease prevention and control in the citrus industry and is expected to help improve the yield and quality of citrus medicinal materials.
Citrus/microbiology* ; Plant Diseases/microbiology* ; Rhizobiaceae/physiology* ; High-Throughput Screening Assays/methods* ; Liberibacter/physiology*

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective:To discuss the effect of acupuncture on the differentiation and apoptosis of quadriceps muscle satellite cells in model rats with knee osteoarthritis(KOA),and to clarify its related mechanism.Methods:A total of 40 SPF-grade rats were selected and randomly divided into control group,model group,celecoxib group,and acupuncture group,with 10 rats in each group.The rats in control group only underwent joint cavity incision followed by suturing,while the rats in model group,celecoxib group,and acupuncture group were used to replicate the KOA models.The maximum circumference of the femoral segment of the affected limb,rat body mass,and quadriceps wet weight of the rats in various groups were measured;the quadriceps wet weight maintenance rate and quadriceps wet weight/body mass ratio of the rats in various groups were calculated.HE staining was used to observe the pathomorphology of articular cartilage and quadriceps muscle tissue of the rats in various groups;terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of interleukin-6(IL-6),Janus kinase(JAK),and signal transducer and activator of transcription 3(STAT3)in quadriceps muscle tissue of the rats in various groups;Western blotting method was used to detect the expression levels of IL-6/JAK/STAT3 signaling pathway proteins,and muscle satellite cells,and apoptosis-related proteins in quadriceps muscle tissue of the rats in various groups.Results:Compared with control group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in model group were significantly decreased(P<0.05);compared with model group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in acupuncture group were significantly increased(P<0.05).The HE staining results showed that the knee articular cartilage of the rats in control group remained intact,chondrocytes were aggregated and horizontally arranged with smooth edges,and quadriceps muscle cells were long cylindrical,orderly arranged,and regular in shape;in model group,the knee articular cartilage was thinner with rough edges,reduced number of cartilage layers,and disordered arrangement,and the quadriceps muscle fibers were disorganized,with some muscle fiber dissolution and muscle cell membrane damage,accompanied by muscle fiber fragments and a large amount of inflammatory exudate;in celecoxib group,the morphology of knee articular cartilage was generally normal,occasionally with irregular cartilage arrangement and reduced thickness,sporadically visible necrotic chondrocytes,quadriceps muscle fibers and sarcolemma were relatively intact,new muscle fibers appeared,some muscle fiber edges were blurred,accompanied by a small amount of cell debris and mild inflammatory infiltration;in acupuncture group,the knee articular cartilage structure remained intact with smooth edges,occasionally rough edges,and chondrocytes were aggregated and orderly arranged.The TUNEL assay results showed that compared with control group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly decreased(P<0.05);compared with celecoxib group,the apoptosis index in articular cartilage and quadriceps muscle tissue of the rats in acupuncture group were significantly decreased(P<0.05).The immunofluorescence assay results showed that compared with control group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of IL-6,JAK,STAT3,paired box transcription factor 7(Pax7),Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).Compared with control group,the expression levels of B-cell lymphoma 2(Bcl-2),B-cell lymphoma-xl(Bcl-xl),and myeloid cell leukemia 1(MCL1)proteins in quadriceps muscle tissue in model group were significantly decreased(P<0.05),and the expression levels of Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)proteins were significantly increased(P<0.05);compared with model group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05);compared with celecoxib group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05).Conclusion:Acupuncture can promote the differentiation of quadriceps muscle satellite cells and inhibit muscle cell apoptosis in the model rats with KOA,and the mechanism may be related to the up-regulation of expressions of IL-6,JAK,and STAT3 proteins in the quadriceps muscle tissue.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.