[Saikosaponin a alleviates pentylenetetrazol-induced acute epileptic seizures in mouse models of depression by suppressing microglia activation-mediated inflammation].

OBJECTIVE: To explore the inhibitory effect of saikosonin a (SSa) on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect. METHODS: Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks, and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole. The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests, epileptic seizure grading and hippocampal morphology observation. ELISA was used to detect blood corticosterone levels of the mice, and RTqPCR was performed to detect the pro- and anti-inflammatory factors. Microglia activation in the mice was observed using immunofluorescence staining. RESULTS: The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level (all P < 0.05). Compared with those with pentylenetetrazole-induced epilepsy alone, the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures, increased number, grade and duration of of seizures, reduced Nissl bodies in hippocampal CA1 and CA3 neurons, increased number of Iba1-positive cells, and significantly enhanced hippocampal expressions of IL-1ß, IL-10, TNF-α and IFN-γ. Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures, reduced the number, duration, and severity of seizures, increased the number of Nissl bodies, decreased the number of Iba1-positive cells, and reduced the expression levels of IL-1ß, IL-10, TNF-α, and IFN-γ in the hippocampus (P < 0.05). CONCLUSION: Depressive state aggravates epileptic seizures, increases microglia activation, and elevates inflammation levels. SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

[Pulse oximetric saturation/fraction of inspired oxygen and partial pressure of oxygen/fraction of inspired oxygen in diagnosing acute respiratory distress syndrome: which is better?]

Acute Respiratory Distress Syndrome (ARDS) is distinguished by hypoxemia, contributing to heightened morbidity, elevated mortality rates, and substantial healthcare expenses, thereby imposing a significant burden on patients and society. Presently, effective treatments for ARDS are lacking, emphasizing the pivotal role of early diagnosis and timely intervention in its successful management. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, P/F) has traditionally served as a crucial metric for assessing patient hypoxemia and disease severity. While relatively accurate, its reliance on advanced technical expertise and specific medical equipment conditions constrains its implementation in areas with underdeveloped medical standards, resulting in missed diagnoses and treatments for ARDS patients. Conversely, the Pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2, S/F) has garnered increasing attention owing to its straightforward, non-invasive, and sustainable monitoring attributes. This article seeks to meticulously compare the correlation, accuracy, and clinical feasibility of S/F with P/F in ARDS diagnosis, so as to propose diagnostic indicators for more quickly and accurately assessing the oxygenation status of ARDS patients.

[Methylthioadenosine phosphorylase and p16 as surrogate diagnostic markers for CDKN2A homozygous deletion in brain tumors].

Objective: To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. Methods: A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined. Results: Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion (P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions: MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

The laminar organization of cell types in macaque cortex and its relationship to neuronal oscillations.

The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6. Here, we investigate whether specific conserved cell types may produce the spectrolaminar motif. We collected laminar histological and electrophysiological data in 11 distinct cortical areas spanning the visual hierarchy: V1, V2, V3, V4, TEO, MT, MST, LIP, 8A/FEF, PMD, and LPFC (area 46), and anatomical data in DP and 7A. We stained representative slices for the three main inhibitory subtypes, Parvalbumin (PV), Calbindin (CB), and Calretinin (CR) positive neurons, as well as pyramidal cells marked with Neurogranin (NRGN). We found a conserved laminar structure of PV, CB, CR, and pyramidal cells. We also found a consistent relationship between the laminar distribution of inhibitory subtypes with power in the local field potential. PV interneuron density positively correlated with gamma (40-150 Hz) power. CR and CB density negatively correlated with alpha (8-12 Hz) and beta (13-30 Hz) oscillations. The conserved, layer-specific pattern of inhibition and excitation across layers is therefore likely the anatomical substrate of the spectrolaminar motif. Significance Statement: Neuronal oscillations emerge as an interplay between excitatory and inhibitory neurons and underlie cognitive functions and conscious states. These oscillations have distinct expression patterns across cortical layers. Does cellular anatomy enable these oscillations to emerge in specific cortical layers? We present a comprehensive analysis of the laminar distribution of the three main inhibitory cell types in primate cortex (Parvalbumin, Calbindin, and Calretinin positive) and excitatory pyramidal cells. We found a canonical relationship between the laminar anatomy and electrophysiology in 11 distinct primate areas spanning from primary visual to prefrontal cortex. The laminar anatomy explained the expression patterns of neuronal oscillations in different frequencies. Our work provides insight into the cortex-wide cellular mechanisms that generate neuronal oscillations in primates.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

Long-term prognostic value of thyroid hormones in left ventricular noncompaction.

PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Positive association between circulating Caveolin-1 and microalbuminuria in overt diabetes mellitus in pregnancy.

AIMS: Mounting evidence has shown that caveolin-1 plays a pathological role in the progression of albuminuria. Our study aimed to provide clinical evidence showing whether circulating caveolin-1 levels were associated with microalbuminuria (MAU) in women with overt diabetes mellitus in pregnancy (ODMIP). METHODS: A total of 150 pregnant women were enrolled in different groups, including 40 women with ODMIP and MAU (ODMIP + MAU), 40 women with ODMIP, and 70 women without ODMIP (Non-ODMIP). Plasma caveolin-1 levels were determined by ELISA. The presence of caveolin-1 in the human umbilical vein vascular wall was evaluated by immunohistochemical and western blot analysis, respectively. Albumin transcytosis across endothelial cells was measured using an established nonradioactive in vitro approach. RESULTS: Significantly increased levels of plasma caveolin-1 were detected in ODMIP + MAU women. The Pearson's correlation analysis revealed a positive correlation between plasma caveolin-1 levels and Hemoglobin A1c (HbA1c %) as well as with MAU in the ODMIP + MAU group. Simultaneously, experimental knockdown or overexpression of caveolin-1 significantly decreased or increased the level of albumin transcytosis across both human and mouse glomerular endothelial cells (GECs), respectively. CONCLUSIONS: Our data showed a positive association between plasma caveolin-1 levels and microalbuminuria in ODMIP + MAU.

Distinguishment between high-grade gliomas and solitary brain metastases in peritumoural oedema: quantitative analysis using synthetic MRI at 3 T.

AIM: To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. MATERIALS AND METHODS: Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1native, T2native, and PDnative) and after (T1post, T2post, and PDpost) contrast agent injection. Student's t-test or the Mann-Whitney U-test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. RESULTS: The mean T1native, T2native, and T1post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p<0.05). The T1post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p<0.05). The combined T1native, T2native, and T1post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. CONCLUSIONS: Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs.

Collision in double-image encryption scheme based on spatial encoding and phase-truncation Fourier transforms.

In this paper, the security strength of a double-image cryptosystem using spatial encoding and phase-truncation Fourier transforms (PTFTs) is evaluated. Unlike the conventional PTFT-based cryptosystem, where two random phase masks (RPMs) are used as public keys to provide enough phase constrains in the estimation, in the improved cryptosystem, the RPM generated by a random amplitude mask (RAM) is treated as an unknown parameter. Due to this fixed RAM, the number of constraints in the estimation decreases to achieve high robustness against potential iterative attacks. Moreover, instead of two phase-only masks (POMs), here the two POMs and the RAM are utilized as the private keys in the improved cryptosystem; thus, the key space of the double-image cryptosystem has been enlarged. However, we noticed that the RAM used to encode plaintexts spatially and to generate the phase encryption key is independent of the plaintexts. This could be recovered by a known pair of plaintexts and the ciphertext. Once the information of the RAM is retrieved, the phase key RPM can also be produced making the cryptosystem vulnerable. Based on this finding, new hybrid algorithms, including a known-plaintext attack and a known key attack are proposed to crack the enhanced PTFT-based cryptosystem. The information of the plaintexts can be retrieved from one POM using the proposed algorithms without any knowledge of another POM and the corresponding ciphertext. Numerical simulations have been carried out to validate the information disclosure problem still exists in the double-image cryptosystem based on spatial encoding and PTFTs.

[A close contact of coronavirus disease 2019 with severe imported malaria: a case report].

This article presents a severe cerebral malaria patient in shock with a close contact of COVID-19 that was successfully cured in a negative pressure ward during the global pandemic of COVID-19. The patient experienced a sudden onset of high fever and coma in a designated isolation hotel after returning from Africa, and was transferred to a designated hospital. Following antimalarial therapy, blood pressure elevation, increase of blood volume, bedside hemodialysis, mechanical ventilation, plasma and platelet transfusions, the case gradual recovered.

[A randomized controlled study on the long-term efficacy of intra-cervical lymphatic immunotherapy for adult allergic rhinitis].

Objective: To determine the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT) for adult allergic rhinitis (AR) by comparing it with subcutaneous immunotherapy (SCIT). Methods: A total of 100 adult AR patients with dust mite allergy in Department of Otorhinolaryngology, First People's Hospital of Foshan from Feb 2018 to Dec 2019 were randomly divided into two groups, 50 in SCIT group [including 42 males and 8 females, aging (32.55±9.72) years] and 50 in ICLIT group [including 45 males and 5 females, aging (31.33±9.84) years]. The changes in total symptom score (total system score, TSS), nasal symptom score (total nasal symptom score, TNSS), eye symptom score (total ocular scoring system, TOSS), drug score (total medication score, TMS), and quality of life score of the two groups of patients were evaluated before and after treatment, and the adverse reactions of all patients during the treatment period were recorded. The changes in the level of dust mite specific IgE (sIgE) in the serum were evaluated. GraphPad Prism 9.0 software was used for statistical analysis. Results: In the SCIT group, 38 patients completed treatment and follow-up, with a dropout rate of 24%. In the ICLIT group, 48 patients completed treatment and follow-up, with a dropout rate of only 4%. The scores of TSS, TNSS, TOSS, TMS, and quality of life in the ICLIT group before treatment were 32.1±3.0, 27.3±3.1, 4.8±2.8, 2.3±0.9, and 68.1±28.7, respectively; After 36 months of treatment, the scores were 21.8±11.4, 18.1±9.4, 3.7±2.9, 1.3±1.1, and 36.0±26.7, respectively, which were significantly lower than those before treatment (all P<0.001). After 36 months of treatment, the TSS of the ICLIT group improved by 10.3±11.2 compared to before, while the TSS of the SCIT group improved significantly by 21.9±11.0 compared to before, with statistically significant differences between the groups (P<0.001). No serious systemic adverse reactions occurred in both groups of patients. Conclusions: ICLIT treatment for adult AR has long-term efficacy, high safety, and high compliance, but its long-term efficacy is not as good as SCIT. ICLIT can be considered as a new complementary option for AR immunotherapy.

Hybrid plaintext attack for a cryptosystem based on interference and the phase-retrieval technique.

In this paper, the security strength of an enhanced cryptosystem based on interference and the phase-retrieval technique is evaluated. The security strength of the optical cryptosystem was improved through the phase-retrieval technique used to generate a phase-only mask (POM) as the ciphertext. Due to the complex mathematical model of the phase-retrieval technique, it seems that a silhouette problem existing in the conventional interference-based scheme was removed. However, we noted that the random phase mask (RPM) regarded as the only private key was fixed in the encryption path, which is not related to the plaintext and makes it possible to be recovered using a known-plaintext attack (KPA). Moreover, we also found that the RPM has high key sensitivity, and it should be recovered precisely to retrieve information of plaintexts during the attack. Thus, a hybrid KPA where three pairs of known plaintexts and their ciphertexts are regarded as the amplitude and phase constraints to obtain the precise estimation of the RPM is proposed. Then, with the help of the estimated private key, information of the original plaintexts encoded using the cryptosystem under study could be retrieved from an arbitrarily given ciphertext without any knowledge of the private key. Our cryptoanalysis shows that the cryptosystem based on interference and the phase-retrieval technique is vulnerable to the proposed attack, and there is a security leak in it. Numerical simulations have been carried out to demonstrate the performance of our proposed attack.

[Clinical characteristics of aplastic anemia patients with abnormal autoantibodies and the impact of autoantibodies on immunosuppressive therapy response].

Objective: To investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST). Method: A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results: A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1∶100, 1∶320, and 1∶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender (OR=1.980, 95%CI 1.206-3.277), older age (OR=1.017, 95%CI 1.003-1.032), and presence of PNH clone (OR=1.875, 95%CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females (OR=1.24, 95%CI 1.02-1.51), severe AA (OR=1.26, 95%CI 1.07-1.47), and age≥40 years (OR=1.26, 95%CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions: Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.

Ru-Based Organometallic Agents Bearing Phenyl Hydroxide: Synthesis and Antibacterial Mechanism Study against Staphylococcus aureus.

The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 µg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.

[The effect of on-demand glucocorticoid strategy on the occurrence and outcome of p-ALG-associated serum sickness in aplastic anemia].

Objective: To investigate the effect of on-demand glucocorticoid strategy on the occurrence and outcome of porcine anti-lymphocyte globulin (p-ALG) -associated serum sickness in aplastic anemia (AA) . Methods: The data of AA patients who received in the Anemia Diagnosis and Treatment Center of Haematology Hospital, CAMS & PUMC from January 2019 to January 2022 were collected. Among them, 35 patients were enrolled in the on-demand group, with the glucocorticoid strategy adjusted based on the occurrence and severity of serum sickness; 105 patients were recruited in the usual group by matching the age and disease diagnosis according to 1∶3 ratio in patients who received a conventional glucocorticoid strategy in the same period. The incidences, clinical manifestations, treatment outcomes of serum sickness, and glucocorticoid dosage between the two groups were analyzed. Results: The incidences of serum sickness in the on-demand group and the usual group were 65.7% and 54.3% (P=0.237) , respectively. The median onset of serum sickness was the same [12 (9, 13) d vs the 12 (10, 13) d, P=0.552], and clinical symptoms and signs, primarily joint, and/or muscle pain, fever, and rash were similar. Severity grades were both dominated by Grades 1-2 (62.8% vs 51.4%) , with only a few Grade 3 (2.9% vs 2.9%) , and no Grades 4-5. No significant difference in the serum sickness distribution (P=0.530) . The median duration of serum sickness was the same [5 (3, 7) d vs 5 (3, 6) d, P=0.529], and all patients were completely cured after glucocorticoid therapy. In patients without serum sickness, the average dosage of prophylactic glucocorticoid per patient in the usual group was (469.48 ±193.57) mg (0 in the on-demand group) . When compared to the usual group, the average therapeutic glucocorticoid dosage per patient in the on-demand group was significantly lower [ (125.91±77.70) mg vs (653.90±285.56) mg, P<0.001]. Conclusions: In comparison to the usual glucocorticoid strategy, the on-demand treatment strategy could significantly reduce glucocorticoid dosage without increasing the incidence of serum sickness; in addition, the duration of serum sickness and the incidence of above Grade 2-serum sickness were similar.

[Metagenomic next-generation sequencing of plasma for the identification of bloodstream infectious pathogens in severe aplastic anemia].

Objective: To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection. Methods: From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy. Results: ①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion: mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

[Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review].

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.