Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Objective: To analyze the relationship between the risk of tuberculosis outbreaks in schools and the visit interval of index cases, so as to provide a scientific reference for predicting the risks of tuberculosis outbreak and making preventive measures. Methods: A total of 630 index cases from school tuberculosis outbreaks were studied during January, 2015 to December, 2022. Data on demographics, consultation history, etiological diagnosis, and methods of detection were collected. Restricted Cubic Splines (RCS), unconditional Logistic regression, and the receiver operating characteristic curve (ROC curve) were used for analysis. Results: The RCS fitted curve showed that the risk of a tuberculosis outbreak linearly increased when the consultation interval for etiologically negative patients exceeded 5.79 days, or for etiologically positive patients exceeded 8.37 days. After multi factor adjustment, for every additional day in the visit interval of the index case, the odds ratio ( OR ) value for a high risk outbreak was 1.10 (95% CI =1.07-1.13)( P <0.05). When analyzed by tertiles of visit intervals, compared to an interval of <14 days, the OR values (95% CI ) for high risk outbreaks in schools with intervals of 14-<28 days and ≥28 days were 10.32(3.04-35.10) and 82.58( 28.42 -239.95), respectively( P <0.01), indicating a trend of increasing outbreak risk with longer visit intervals. Based on the ROC curve analysis, the optimal threshold for predicting a high risk school tuberculosis outbreak was 23.5 days, with an area under the curve ( AUC ) of 0.93 (95% CI =0.89-0.98). Conclusion An extended visit interval of index cases is a good early warning indicator for high risk tuberculosis outbreaks in schools and could be considered a key factor in early intervention and risk control strategies.

Objective:To investigate the changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:The clinical data of 99 DLBCL patients admitted to the First Affiliated Hospital of Xiamen University from January 2022 to January 2023 were retrospectively analyzed. T lymphocyte subsets in peripheral blood before and after treatment were detected by using flow cytometry. According to the disease status at the time of blood collection and detection, the patients were divided into the newly-diagnosed DLBCL group (28 cases), and the newly-treated remission DLBCL group (71 cases); and 40 healthy volunteers undergoing the physical examination during the same period were selected as the healthy control group. The proportion and absolute count differences of T lymphocytes and the related subsets in 3 groups were compared. Besides, the correlation among T lymphocyte subsets, the correlation of each subset with international prognostic index (IPI) score and treatment response in newly-diagnosed DLBCL patients were further analyzed.Results:The proportion of CD3 + T cells in newly-diagnosed DLBCL group was decreased compared with that in the healthy control group [(58±14)% vs. (67±7)%, P < 0.05]. The absolute count of CD3 + T cells in both newly-diagnosed group and the newly-treated remission group was reduced compared with that in the healthy control group [(875±483) /μl and (808±553) /μl vs. (1 374±279) /μl, P < 0.001]. The absolute count of CD4 + and CD8 + T cells in newly-diagnosed group was decreased compared with that in the healthy control group [(478±313) /μl vs. (695±154) /μl, (316±181) /μl vs. (525±193) /μl, all P < 0.001]. Both the proportion and absolute count of CD4 + T cells in the newly-treated remission DLBCL group were decreased compared with those in the newly-diagnosed DLBCL group and the healthy control group [(40±14)% vs. (53±14)% and (51±9)%, (313±247) /μl vs. (478±313) /μl and (695±154) /μl, all P < 0.05]. The porportion of CD8 + T cells was increased compared with that in the other two groups [(51±15)% vs. (37±12)% and (38±9)%, all P < 0.001]. Compared with the healthy control group, the effect/memory subsets proportion of regulatory T cell (Treg) and conventional T cell (Tcon) were increased in both newly-diagnosed DLBCL group and the newly-treated remission DLBCL group [(79±16)% and (84±12)% vs. (71±11)%,(72±16)% and (76±14)% vs. (62±13)%, all P < 0.05], and the proportion of CD127 + memory Tcon and CD8 + T cell subsets was reduced [(73±14)% and (66±20)% vs. (85±8)%,(39±15)% and (25±21)% vs. (62±16)%, all P < 0.05]. In newly-diagnosed DLBCL group, the absolute counts of CD3 + T and CD4 + T cells were negatively correlated with the proportion of effector Treg ( r = -0.379, P = 0.049; r = -0.384, P = 0.040, respectively). IPI score of DLBCL patients was correlated with the proportion of CD8 + T cells ( Eta2 = 0.15, P = 0.038). The proportion of CD127 + memory Tcon in patients with non-complete remission was increased compared with that in patients with complete remission after treatment ( P = 0.020). Conclusions:The proportion and absolute count of T lymphocyte cells in peripheral blood of newly-diagnosed DLBCL patients is decreased, and the differentiation state of T lymphocyte cells shows change trend, which is related to the clinical characteristics and treatment response of DLBCL patients. Even if DLBCL patients have achieved treatment remission, T lymphocyte cells are not completely return to the normal.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To investigate the efficacy and safety of posaconazole in the prevention of invasive pulmonary aspergillosis (IPA) in patients with liver failure treated with glucocorticoids (GC).Methods:The study was an observational study. Patients with early and middle stages of liver failure hospitalized in the Department of Infectious Diseases of Hebei Medical University Third Hospital, who received GC treatment between February 2016 and February 2022 were included. The patients were divided into trial group (with posaconazole suspension (200 mg each time, three times daily)) and control group (without posaconazole) according to whether posaconazole was used during treatment. Two groups of patients were matched of 1∶2 ratio according to age, gender and baseline model for end-stage liver disease (MELD) score. The basic information, laboratory examination results, adverse reactions of posaconazole, incidence of invasive Aspergillus infection and therapeutic effect of patients were collected. Statistical analysis was performed using the chi-square test, logistic regression analysis was used to screen risk factors for IPA, the receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the risk factors, Kaplan-Meier survival curves was used to analyze patient′s survival, and Log-rank test was used to compare the survival rates between the trial group and control group. Results:A total of 108 patients (36 in trial group and 72 in control group) were enrolled. There were no statistical differences between the two groups in terms of the etiology of liver diseases, baseline laboratory findings and risk factors for invasive Aspergillus infection (all P>0.05). There were 21 cases of IPA during hospitalization, with a total infection rate of 19.4%(21/108), including 5.6%(2/36) in the trial group and 26.4%(19/72) in the control group. The difference of IPA incidences between the two groups was statistically significant ( χ2=6.65, P=0.010). Logistic regression analysis suggested that elevated C-reactive protein, GC application more than seven days and cumulative dose of GC were independent risk factors for IPA in patients with liver failure treated with GC (odds ratio ( OR)=1.080, 15.266, 1.004, respectively, all P<0.05). The ROC curve showed that the cut-off value of C-reactive protein was 6.00 mg/L, and cumulative dose of GC was 490 mg. There were no statistical differences between the two groups in terms of adverse effects such as neutropenia, thrombocytopenia, gastrointestinal bleeding, nausea and vomiting rates (all P>0.05), and there were no patients with visual disturbances or discontinuation of medication. Cumulative deaths were 20(18.5%), and 88(81.5%) patients survived in this study. There were 11(52.4%) deaths among 21 patients with IPA and nine (10.3%) deaths among 87 patients without IPA. The difference of survival rates between patients who developed and did not develop IPA was statistically significant ( χ2=21.31, P<0.001). Conclusions:Posaconazole may be helpful in reducing the incidence of concurrent IPA morbidity in patients with liver failure treated with GC, thereby improving survival rates with few adverse effects.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To explore expressions of interleukin 6 (IL-6), interleukin 8 (IL-8) and interleukin 10 (IL-10) in the peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL) and their clinical significances.Methods:The clinical data of 78 newly diagnosed patients with DLBCL from March 2018 to March 2021 in the First Affiliated Hospital of Xiamen University were retrospectively analyzed, and 58 healthy people receiving physical examination during the same period were taken as the healthy controls. The expressions levels of IL-6, IL-8 and IL-10 in peripheral blood were tested by using cytometric bead array (CBA), and the association of the levels of IL-6, IL-8 and IL-10 with clinical characteristics, disease staging and prognosis was analyzed.Results:The expression levels of IL-6, IL-8 and IL-10 in DLBCL group were higher than those in the healthy control group [(171.81±70.91) pg/ml vs. (2.71±0.28) pg/ml, (47.95±13.04) pg/ml vs. (3.69±0.47) pg/ml, (38.02±10.35) pg/ml vs. (1.77±0.23) pg/ml], and differences were statistically significant ( t values were 2.38, 3.39, 3.50, all P<0.05). In DLBCL group, the expression levels of IL-6, IL-8 and IL-10 in patient with bone marrow invasion, international prognostic index (IPI) 3-5 scores and clinical staging Ⅲ-Ⅳ were higher than those in patients with bone marrow non-invasion, IPI 1-2 scores and clinical stagingⅠ-Ⅱ(all P<0.05). There was a relationship between the expression levels of IL-6 and IL-8, IL-6 and IL-10, IL-8 and IL-10 in peripheral blood of DLBCL patients ( r2 value was 0.93, 0.89, 0.89, respectively; all P < 0.05). Among patients with high expressions of IL-6, IL-8 and IL-10, the proportion of patients not receiving remission after 6 cycles of treatment in clinical staging Ⅲ-Ⅳ was higher than that of patients with high expressions of IL-6, IL-8 and IL-10 alone or any two of them, and differences were statistically significant (all P < 0.05). Conclusions:There is a high correlation of IL-6, IL-8 and IL-10 expression levels; the increasing expression levels of them may predict the later disease stage and poor prognosis for DLBCL patients.

Objective:To investigate the safety and therapeutic effect of Shakubatrivalsartan in the treatment of pediatric dilated cardiomyopathy.Methods:Clinical information, treatment and prognosis of 5 cases with dilated cardiomyopathy in the First Affiliated Hospital of Xinxiang Medical University from June 2018 to December 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:A total of 5 cases of children with dilated cardiomyopathy were analyzed, including 3 males and 2 females with age of 12-17 years.Their median left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVDd), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 37% (20%-41%), 61 mm (59-67 mm), and 13 250 ng/L (12 310-21 823 ng/L), respectively.The median conventional treatment time was 5 months (1-12 months), in which, the condition of heart failure gradually progressed, and the median LVEF, LVDd and NT-proBNP levels were reduced to 33% (19%-37%), 61 mm (60-74 mm), 13 144 ng/L (8 086-15 137 ng/L). After less than 3 months of follow-up following conventional treatment plus Shakubatrivalsartan, NT-proBNP level significantly decreased in 5 cases.Besides, 4 cases had improved cardiac function, and the other one′s improvement was not obvious.The blood pressure of 5 cases decreased at varying degrees after medication of Shakubatrivalsartan, which should be closely monitored during drug titration.No adverse reactions were reported.Conclusions:Shakubatrivalsartan for the treatment of pediatric dilated cardiomyopathy is safe and effective, which can alleviate or reverse the process of myocardial remodeling and improve cardiac ejection fraction, thus improving the prognosis.