[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

The advent of bruton tyrosine kinase inhibitors (BTKi) has offered more therapeutic choices for patients with B-cell malignancies. However, with its widespread application in recent years, the use of BTKi increases the risk of severe infections in patients. Here, we report three cases of B-cell malignancies, including one case of chronic lymphocytic leukemia and two cases of diffuse large B-cell lymphoma. During treatment with BTKi zanubrutinib, different degrees of invasive fungal disease (IFD) of the central nervous system occurred in these patients. All patients fully recovered following antifungal therapy. With a median follow-up of 35 months, all patients remained in a continuous remission state, and none of them had a recurrence of IFD.

The advent of bruton tyrosine kinase inhibitors (BTKi) has offered more therapeutic choices for patients with B-cell malignancies. However, with its widespread application in recent years, the use of BTKi increases the risk of severe infections in patients. Here, we report three cases of B-cell malignancies, including one case of chronic lymphocytic leukemia and two cases of diffuse large B-cell lymphoma. During treatment with BTKi zanubrutinib, different degrees of invasive fungal disease (IFD) of the central nervous system occurred in these patients. All patients fully recovered following antifungal therapy. With a median follow-up of 35 months, all patients remained in a continuous remission state, and none of them had a recurrence of IFD.

The diagnosis and treatment resources for rare diseases in China are highly imbalanced. The basic diagnosis and treatment capabilities are weak, the diagnosis period for patients is long, and the rates of missed diagnosis and misdiagnosis are relatively high. The establishment of a hierarchical diagnosis and treatment system is the inevitable approach to enhancing the diagnosis and treatment standards of rare diseases. Currently, the implementation of the domestic hierarchical diagnosis and treatment system for rare diseases still confronts numerous challenges, such as ambiguous referral standards and processes of primary medical institutions, and ineffective information interaction among institutions at all levels. Thus, it is essential to facilitate high-level information construction for the hierarchical diagnosis and treatment of rare diseases. This paper explores the process of constructing a multidisciplinary joint remote diagnosis and treatment platform and a health management platform through informatization, with the hope of establishing two closed loops of digital diagnosis and treatment services and health follow-up management for patients with rare diseases, as well as achieving timely diagnosis and lifelong health management for patients. It integrates and optimizes auxiliary diagnostic tools, promotes the rapid dissemination of rare disease diagnosis and treatment experiences to the grassroots, enhances the information construction level of the hierarchical diagnosis and treatment system, and endeavors to address the practical predicament of weak diagnosis and treatment capabilities of rare diseases in grassroots medical institutions. Additionally, this paper proposes an essential approach for multi-dimensional independent innovation to guide the popularization of efficient and high-quality rare disease diagnosis and treatment services. By encompassing innovating the rare disease diagnosis and treatment collaboration network and multidisciplinary diagnosis and treatment model, facilitating the application of the latest biomedical and informatics technologies to the grassroots, and constructing a national intelligent data platform for rare disease innovation, a new model for rare disease services with Chinese characteristics will be established. This will significantly enhance the medical treatment level of rare diseases in China and strive for more benefits for patients.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

Objective:To evaluate the influence of the sleeve lengths and implant lengths on accuracy of static computer-assisted implant surgery (sCAIS).Methods:Twenty-eight models of bilateral mandibular single tooth loss were included. Fifty-five implants were placed under the guidance of sCAIS (Straumann Bone Level 4.1 mm×10 mm). According to the height of metal sleeve of static guide plate, 55 implants were divided into 11 groups (free hand group, 1 mm group, 2 mm group, 3 mm group, 4 mm group, 5 mm group, 6 mm group, 7 mm group, 8 mm group, 9 mm group, 10 mm group), with 5 implants in each group. Eight research models were included. Group with 5 mm sleeve guides were used to place implants of different length, (Straumann Bone Level width 4.1 mm, height was 8 mm, 10 mm and 14 mm), 5 implants in each group. Eighteen patients with mandibular single tooth loss were included in the Department of Oral Implantology, Tianjin Stomatological Hospital from October 2018 to June 2019. There were 10 males and 8 females, 18-46(33.7±7.9) years old. A total of 18 implants were implanted and divided into 3 groups (free hand group, 3 mm group and 5 mm group) with 6 implants in each group. Digital software was used to compare the implant positions before and after implantation. Non-parametric Kruskal-Wallis test or one-way ANOVA were used to analyze the results.Results:There was no significant difference in implant vertical deviation between different sleeve height groups (1-10 mm) and free hand group, but the neck deviation in free hand group[(1.04±0.13) mm] was significantly higher than that in different sleeve height groups (1-10 mm) ( P<0.05). The tip deviations of free hand group, 1 mm group and 2 mm group [(1.32±0.43), (0.83±0.10) and (0.78±0.11) mm, respectively] was significantly higher than that of 10 mm group [(0.31±0.14) mm]( P<0.05). The angle deviation of free hand group and 1 mm group (3.99°±0.85° and 2.59°±0.69°), respectively] was significantly higher than that of 10 mm group (0.61°±0.03°) ( P<0.05). The tip deviations of implants in the 14 mm group [(0.83±0.22) mm] was significantly higher than that in the 8 mm and 10 mm groups [(0.44±0.07) and (0.49±0.06) mm, respectively]. Clinical studies showed that there was no significant difference in neck deviation, tip deviation and angle deviation between 3 mm group and 5 mm group ( P>0.05), but deviations were significantly lower than those in free hand group ( P<0.05). Conclusions:The length of the sleeves has significant influence on the accuracy of the surgical guide. There was no significant difference in accuracy of the implant guide with 3 mm or 5 mm metal sleeves. The vitro study has some limitations and needs further systematic research.

Objective To investigate the phenotypic and functional properties of in vitro-induced He-lios+regulatory T cells(Helios+iTreg) and to analyze the differences between Helios+iTreg and Helios+thymic-derived natural Treg (Helios+nTreg). Methods CD4+CD25- effector T cells (CD4+CD25- Teff) that were separated from healthy subjects were cultured with anti-CD3 and anti-CD28 antibodies and stimulated with IL-2 and TGF-β to induce the generation of Helios+iTreg. Flow cytometry and real-time PCR were respectively used to analyze the differences in phenotype and CpG methylation in Treg-specific demethylated region (TSDR) be-tween Helios+iTreg and Helios+nTreg derived from the same donor. Results CD45RA was highly expressed on Helios+iTreg, but not on Helios+nTreg. Additionally, Helios+iTreg expressed significantly higher levels of CD127,ICOS and PD-1,but lower levels of CXCR3,CCR4 and CD25 than Helios+nTreg did. IFN-γ and IL-2 that expressed by Helios+iTreg were more than those by Helios+nTreg. It was also found that the level of CpG methylation in TSDR was much higher in Helios+iTreg than in Helios+nTreg. Conclusion Both nTreg and iTreg expressed Helios,but the phenotypic and functional properties of the two Treg subsets were different. It was suggested that Helios+iTreg and Helios+nTreg might play different roles in the immune system.

Objective To evaluate values of Serum IgG 4,IgG4/IgG ratio,and IgG4/IgG1 ratio for distinguishing Mikulicz′s disease(MD)from primary Sj?gren′s syndrome(pSS).Methods It retrospectively analyzed 186 patients subjected to serum IgG subclass testing to differentiate MD from primary Sj?gren′s syndrome(pSS)at Peking University People′s Hospital from July 2012 to July 2016.This sample included 42 MD patients and 144 pSS patients.Serum IgG subclass concentrations were measured using Siemens reagents with nephelometry and BNⅡinstrument.In partial patients,serum antinuclear antibodies (ANA)were detected by indirect immunofluorescence assay, and serum anti-SSA antibodies and anti-SSB antibodies were detected by Western blot.Serum IgG subclass test results,ANA test results,serum anti-SSA antibody,and anti-SSB antibody test results were collected.The quantitative data were represented by median(quantile range).The Mann-Whitney U test was used to compare the medians between the two groups.Categorical variables were analyzed with a χ2test and were shown as percentages.The ROC curve was constructed to identify the optimal cut-off values and the area under the curve(AUC)values of the serum IgG4,IgG4/IgG ratio,and IgG4/IgG1 ratio for distinguishing MD patients from pSS patients.Results The medians of serum IgG4, IgG4/IgG ratio and IgG4/IgG1 ratio in MD patients were 11 200 mg/L(17 330),0.444(0.314)and 1.318(1.920), as compared with 329 mg/L(490),0.016(0.025)and 0.023(0.039)respectively in pSS patients(Z=-9.368, -9.560, and -9.571, respectively, P<0.001).For distinguishing MD from pSS, the optimal cut-off values of serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio were 1 870 mg/L,0.111, and 0.206, respectively.The corresponding AUC values were 0.976,0.985,and 0.986,respectively.Comparison of the ROC curves showed that there was no significant difference between AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio(Z=0.283, P=0.777).But AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio were significantly higher than AUC of serum IgG 4(Z=2.360 and 1.975,repectively,P=0.018 and 0.048,respectively).The positive rates of serum ANA in MD and pSS group were 10%and 85.8%,respectively(χ2=71.340,P<0.001).The positive rates of anti-SSA antibody and anti-SSB antibody in MD were 6.7%and 0%,respectively.Compared to 72.3%and 38.3%in pSS group, they were lower(χ2=44.773 and 16.792, P<0.001).Conclusions Measurements of serum IgG4 concentration,IgG4/IgG ratio, and IgG4/IgG1 ratio were of important values in differentiating MD from pSS.Serum IgG4/IgG ratio or IgG4/IgG1 ratio was superior to serum IgG4.

AIM:To explore whether histamine can regulate the expression of early growth response factor-1 (Egr-1) in the cerebral cortex astrocytes.METHODS:Normal wild-type (WT) mice, histidine decarboxylase knockout ( HDC-KO) mice and histamine treated HDC-KO mice were sacrificed for extracting the total RNA of the cerebral cortex. Primary cultured rat cortical astrocytes were treated with histamine at concentrations of 10 -8 , 10 -7 , 10 -6 , 10 -5 or 10 -4 mol/L for 15, 30, 60, 120 or 240 min.H1 or H2 receptor antagonists were pretreated for 15 min before histamine treat-ment.After histamine treatment, the cell total RNA or protein was extracted.The expression of Egr-1 at mRNA and protein levels was determined by real-time PCR and Western blot.RESULTS:The mRNA level of Egr-1 in cerebral cortex of HDC-KO mice was significantly lower than that in WT mice, while exogenous histamine induced the mRNA expression of Egr-1 in HDC-KO mice.In cultured astrocytes, histamine induced the mRNA expression of Egr-1.The maximum increase in the mRNA level of Egr-1 was produced by histamine at concentration of 10 -5 mol/L.In addition, histamine-induced Egr-1 mRNA accumulation peaked at 30 min after commencing stimulation, while histamine significantly increased Egr-1 protein expression at 60 min.Furthermore, histamine-induced Egr-1 expression was inhibited by H1 receptor antagonist but not H2 receptor antagonist.CONCLUSION:Histamine up-regulates the Egr-1 expression in cerebral cortex and cultured astrocytes, which may attribute to H1 receptor activation.

AIM: To determine the effect of endogenous histamine on transient forebrain ischemia-induced neuronal injury at the late phase of reperfusion using histidine decarboxylase knockout ( HDC-KO) mice.METHODS:Wild-type (WT) and HDC-KO mice were subjected to bilateral common carotid artery occlusion for 30 min followed by 3 d or 15 d of reperfusion.At different time points after reperfusion, the body weight, mortality rate, learning and memory in fear conditioning test and hippocampal CA 1 neuronal density were evaluated .RESULTS: At 1 d after reperfusion , the body weight loss was observed in both WT and HDC-KO mice.At 4 d, 5 d, 6 d and 7 d after reperfusion, the increment in the body weight of the HDC-KO mice was significantly smaller than that of the WT mice .During the period between 8 d and 14 d after reperfusion, the mortality rate of the HDC-KO mice was higher than that of the WT mice (P<0.05).At 14 d after reperfusion , the HDC-KO mice exhibited more aggravated deficits in contextual and cue memory compared with the WT mice.Correspondingly , a more severe CA1 neuronal injury in the HDC-KO mice than that in the WT mice was ob-served at 15 d but not at 3 d after reperfusion (P<0.05).CONCLUSION:Endogenous histamine may attenuate learn-ing/memory deficits and neuronal injury at the late phase of ischemia /reperfusion.However, the involved mechanisms need to be further investigated .