Comparison of human leukocyte antigen in patients with paroxysmal nocturnal hemoglobinuria of different clone sizes.

Glycosylphosphatidylinositol-anchored protein-deficient hematopoietic stem and progenitor cell development caused by PIGA mutations cannot fully explain the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH). Herein, patients newly diagnosed with PNH at our hospital between April 2019 and April 2021 were recruited. The human leukocyte antigen (HLA) class I and II loci were analyzed, and patients were stratified by PNH clone sizes: small (< 50%) and large (≥ 50%). In 40 patients (29 males; 72.5%), the median PNH clone size was 72%. Thirteen (32.5%) and twenty-seven (67.5%) patients harbored small and large PNH clones, respectively. DRB1*15:01 and DQB1*06:02 had higher frequencies in patients with PNH than in healthy controls (adjusted P-value = 4.10 × 10-4 and 4.10 × 10-4, respectively). Whole HLA class I and II allele contributions differed (P = 0.046 and 0.065, not significant difference) when comparing patients with small and large PNH clones. B*13:01 and C*04:01 allelic frequencies were significantly higher in patients with small clones (P = 0.032 and P = 0.032, respectively). Patients with small clones had higher class II HLA evolutionary divergence (HED) (P = 0.041) and global class I and II HED (P = 0.019). In the entire cohort, 17 HLA aberrations were found in 11 (27.5%) patients. No significant differences in HLA aberrations were found between patients with small or large clones. In conclusion, patients with small clones tended to have a higher frequency of immune attack-associated alleles. A higher HED in patients with small clones may reflect a propensity for T cell-mediated autoimmunity. HLA aberrations were similar between patients with small and large clones.

Treatment of myelofibrosis with refractory anemia with luspatercept: a multicenter Chinese study.

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

Geographic Access to Primary Healthcare Services among Latinos/as/x in Western Alabama.

OBJECTIVES: Alabama's Latino/a/x population grew 278% from 2000 to 2018. Tuscaloosa County, located in the largely rural region of western Alabama, also experienced a significant influx of Latino/as/x during this time frame. Geographic healthcare access (GHA) to primary care and hospitals is crucial for immigrant Latino/as/x to care for their health, but few studies have characterized it. The goals of this article were to describe the availability (defined as number of provider locations) and accessibility (defined as travel impedance between potential patients and provider locations) of primary healthcare services and to discuss potential strategies to address these healthcare access challenges. METHODS: We drew data from the US Census Bureau, American Community Survey 5-year estimates, Blue Cross Blue Shield national doctor and hospital finder database, the Alabama Department of Public Health, and Tuscaloosa Transit Authority. We used geographic data, geographic information systems, and spatial analyses to characterize the availability and accessibility of primary care services and hospitals for Latinos/as/x in Tuscaloosa County using ESRI, ArcGIS 10.6.1. We showed the distribution of Latinos/as/x by census tract with choropleth mapping and mapped primary healthcare providers alongside public transit routes and hospital driving times to support our findings. RESULTS: This work demonstrated that Latinos/as/x in Tuscaloosa County were concentrated in more rural areas surrounding the county's city center, presenting significant barriers to GHA. These areas had fewer primary care providers and limited public transit. Many Latinos/as/x in this county had to travel ≥45 minutes to a hospital. CONCLUSIONS: Outreach and technology-based approaches, including home visit programs, mobile health units, and telemedicine, may be particularly important in bridging the GHA gaps for this and other largely rural populations the southeastern United States. Some of this potential was unlocked during the coronavirus disease 2019 crisis. These gains should be leveraged toward sustainable healthcare access initiatives for rural Latino/a/x populations.

Use of trastuzumab in treating breast cancer during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Trastuzumab is currently the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, it is not recommended for HER2-positive breast cancer patients during pregnancy as it may jeopardize safety of the fetus. Nevertheless, there is evidence that fetuses exposed to trastuzumab in early stages of pregnancy remain healthy METHODS: To evaluate the possible effects of trastuzumab on fetus and provide evidence on the safety of trastuzumab in early pregnancy in HER2-positive breast cancer patients, we analyzed 22 studies involving 22 pregnant women and 23 fetuses. RESULTS: Based on the meta-analysis, the gestational week of exposure to trastuzumab is 0-34 weeks, the average duration of use is 17 weeks, and the average gestational week of delivery is 34.3 weeks. Complications occurred in 77.27% of patients during pregnancy and 56.52% of newborns。The main complication during pregnancy was anhydramnios (68.18%), while the main complications at birth were Respiratory distress or tachypnea (30%). After an average of 25.28 months of follow-up, 17.39% (4/23) of the children died. There was no complication during pregnancy or at birth in patients treated with trastuzumab during early pregnancy (P = 0.043). Patients older than 30 who received trastuzumab during pregnancy were more likely to have neonatal complications (OR = 7.778, 95%CI = 1.2-50.424, P = 0.04). CONCLUSION: These results suggest that trastuzumab use during pregnancy can cause pregnancy,fetal and newborn complications. However, exposed to trastuzumab only in the first trimester are less likely to have pregnancy and fetal complications. Patients with gestational age below 30 years are less likely to have neonatal complications after trastuzumab during pregnancy. Terminating pregnancy should not be the only option for such patients. But more evidence is needed to verify this conclusion.

Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36,480 cases.

BACKGROUND: The survival outcomes of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) for patients with triple-negative breast cancer (TNBC) remain unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of NACT versus ACT in TNBC. METHODS: A systematic search was performed on the PubMed and Embase databases to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC. RESULTS: A total of nine studies involving 36,480 patients met the selection criteria. Among them, 10,728 (29.41%) received NACT, and 25,752 (70.59%) received ACT. The pathological complete response (pCR) rate was 35% (95% CI = 0.23-0.48). Compared with ACT, the overall survival (OS) of NACT was poor (HR = 1.59; 95% CI = 1.25-2.02; P = 0.0001), and there was no significant difference in disease-free survival (DFS) between the two treatments (HR = 0.85; 95% CI = 0.54-1.34; P = 0.49). NACT with pCR significantly improved the OS (HR = 0.53; 95% CI = 0.29-0.98; P = 0.04) and DFS (HR = 0.52; 95% CI = 0.29-0.94; P = 0.03), while the OS (HR = 1.18; 95% CI = 1.09-1.28; P < 0.0001) and DFS (HR = 2.36; 95% CI = 1.42-3.89; P = 0.0008) of patients with residual disease (RD) following NACT were worse compared to those receiving ACT. CONCLUSION: These findings suggest that, for TNBC, NACT with pCR is superior to ACT in improving OS and DFS, and it turns to be opposite when patients are receiving NACT with RD.

Matrilysin-2 expression in colorectal cancer is associated with overall survival of patients.

Tumor recurrence and metastasis are pressing issues of patients with colorectal cancer who receive surgery. Matrilysin-2 (MMP-26) has been proved to play an important role during invasion and metastasis of some human solid tumor. We aimed to investigate the clinical significance and prognostic value of matrilysin-2 in human colorectal cancer. Colorectal cancer and adjacent normal samples from 201 patients were collected. Matrilysin-2 expression level was investigated by immunohistochemistry assay, and its association with overall survival of patients was analyzed by statistical analysis. Results showed that matrilysin-2 expression level significantly elevated in colorectal cancer compared with adjacent normal specimens. Matrilysin-2 expression was also found to be associated with cancer invasion, lymph node metastasis, distant metastasis, and TNM stage. In addition, survival analysis showed that elevated matrilysin-2 expression was associated with poor overall survival of patients. Cox's proportional hazards model indicated that matrilysin-2 was an independent prognostic marker for patients with colorectal cancer. The present study found that the expression of matrilysin-2 increased in colorectal cancer and was associated with tumor progression. It also provided the first evidence that matrilysin-2 expression was an independent prognostic factor for patients with colorectal cancer, which might be a high specific biomarker for colorectal cancer.

Oncogenic miR-106b-5p promotes cisplatin resistance in triple-negative breast cancer by targeting GDF11.

BACKGROUND: Cytoplatin (CDDP) is a standard treatment for triple-negative breast cancer (TNB), but patient resistance to CDDP limits its efficacy. A growing study confirms that microRNAs (miRNAs) are significantly important in breast cancer, especially TNBC. This research was carried out to examine the function of miR-106b-5p in CDDP resistance of TNBC as well as the downstream mechanism. METHODS: The miR-106b-5p and growth-differentiation factor 11 (GDF11) expressions in the tissues from TNBC patients and CDDP-treated TNBC cell lines were measured by RT-qPCR. Thereafter, cell proliferation and migration in the presence of CDDP treatment were evaluated via CCK-8 and Transwell assays in the TNBC cells. A xenograft mice model was also established to verify the miR-106b-5p silencing effect on the growth of CDDP resistance TNBC cells in vivo. Luciferase reporter experiments were performed to predict the relationship between miR-106b-5p and GDF11 expression. RESULTS: The results showed that miR-106b-5p was upregulated in the TNBC tumor cells and TNBC cells treated with CDDP and knockdown of this caused inhibition of the TNBC cell lines' proliferation, migration and suppressed the growth of the TNBC xenografted tumors, in the presence of CDDP treatment. In addition, it was observed that miR-106b-5p can bind to GDF11; as a result in the TNBC tissues and CDDP-treated TNBC cell lines the down-regulation of GDF11 was observed. Moreover, GDF11 silencing promoted CDDP-treated TNBC cell lines' proliferation and migration and reversed the interference effect of miR-106b-5p. CONCLUSIONS: MiR-106b-5p was upregulated in TNBC and this upregulation may promote CDDP resistance of the TNBC cells by targeting GDF11 and inhibiting its expression.

Acupoint transplantation versus non-acupoint transplantation using autologous peripheral blood mononuclear cells in treating peripheral arterial disease.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation-free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%-94.1% vs 78.5%, 95% CI: 66.7%-92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

Pan-Cancer Bioinformatics Indicates ZNF207 is a Promising Prognostic Biomarker and Immunotherapeutic Target.

In the era of personalized cancer treatment, understanding the complexities of tumor biology and immune modulation is paramount. This comprehensive analysis delves into the multifaceted role of Zinc Finger Protein 207 (ZNF207) in pan-cancer, shedding light on its involvement in tumorigenesis, immune evasion, and therapeutic implications. Through integrated genomic and clinical data analysis, we reveal consistent upregulation of ZNF207 across diverse cancer types, highlighting its potential as a prognostic marker and therapeutic target, particularly for liver cancers. Notably, ZNF207 demonstrates intricate associations with clinical-pathological features, immune subtypes, and molecular pathways, indicating its pervasive influence in cancer biology. Furthermore, our study uncovers ZNF207's involvement in immune escape mechanisms, suggesting its potential as a modulator of immune responses within the tumor microenvironment. These findings underscore the significance of ZNF207 in shaping cancer progression and immune landscape, presenting promising avenues for targeted therapy and immunomodulation. Recognizing ZNF207's multifaceted contributions to cancer progression and immune evasion suggests its central role in understanding tumor immunology, beyond mere therapeutic targeting. Nevertheless, further mechanistic studies are imperative to elucidate ZNF207's precise molecular mechanisms and therapeutic implications in cancer treatment. This study primarily utilized various bioinformatics tools such as TIMER 2.0, cProSite, UALCAN, SangerBox, GEPIA2, TISIDB and TIDE to analyze the expression of ZNF207 in multiple cancer samples from the TCGA database.

High- vs regular-dose recombinant human thrombopoietin plus cyclosporine A in patients with newly diagnosed non-severe aplastic anemia: a retrospective cohort study.

BACKGROUND: Cyclosporine A (CsA) and regular doses of recombinant human thrombopoietin (rhTPO) can accelerate platelet recovery in patients with non-severe aplastic anemia (NSAA). However, it is unclear whether CsA plus rhTPO at a higher dose can further increase the efficacy. METHODS: Data from patients with newly diagnosed NSAA, who had been treated with CsA in combination with different doses of rhTPO between February 2021 and August 2021 at Peking Union Medical College Hospital, were reviewed. All the enrolled patients had been treated with CsA at 3-5 mg/(kg/d), and patients were further classified into high-dose (with rhTPO 30000U qd × 14 days for 2 months) group or regular-dose (with rhTPO 15000U qd × 7days for 3 months) group. The treatment response and therapy-related adverse events were compared. RESULTS: 36 patients including 16 (44.4%) in the high-dose and 20 (55.6%) in the regular-dose group were enrolled. The baseline characteristics were compatible between the two groups. The platelet counts were significantly higher at 1/3/6 months in the high-dose group (p = 0.028, 0.0063 and p = 0.040, respectively). The high-dose group had a significantly shorter time to platelet transfusion independence ([1 (0.5-6) months vs 2.5 (1-12) months, p = 0.040]). There was no significant difference in overall response and complete response rate between the two groups at 1/3/6/12 months (p > 0.05). Treatment-related morbidities were similar between the two groups (p > 0.05). CONCLUSIONS: Adding a higher dose of rhTPO can further accelerate platelet recovery and platelet transfusion independence in patients with newly diagnosed NSAA.

Examining the existing usage gap of electronic health records in the United States: A study of National Health Survey.

Background: Little is known about the extent of geographic variation in online health record usage and related demographic characteristics in the United States. Methods: In order to examine geographical variation in the usage of online e-health records (EHR) patient portals in the US, and the sociodemographic factors effects on the access and use of the EHR patient's portal. This study using data from the 2019 and 2020 Health Information National Trends Survey. Specifically, predictors associated with accessing patients' EHR portal were examined. Furthermore, geographic variation of EHR portal' availability and usage gap were examined and mapped. Results: Respondents had significantly higher likelihood to access EHR portals when they are higher educated, willing to seek health information online, insured and had regular providers (adjusted OR = 2.01, 95% CI: 1.44 - 2.80; adjusted OR = 3.51, 95% CI: 2.49 - 4.94; adjusted OR = 2.38, 95% CI: 1.05 - 5.43; adjusted OR = 2.1, 95% CI: 1.51 - 2.92, respectively). Individuals living in Central-West, South regions or other non-urban areas as well as deprived urban areas are less likely to access their EHR portals (adjusted OR = 0.6, 95% CI: 0.41 - 0.89). Furthermore, we found that people living in the Midwest, Southern regions, and Mountain rural areas are more likely to have greater difficulties to access EHR than other regions. Therefore, populations residing in these underserved (deprived urban, rural or remote) areas tend to face more considerable obstacles to e-healthcare. Conclusions: Improve the disparities, accessibility, and educational initiatives on the usage of eHealth resources and encouragement from both healthcare providers and policymakers should be implemented with a particular focus on targeting non-urban areas and underserved population.

Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study.

Aplastic anemia (AA) secondary to radiotherapy presents a difficult situation in the treatment of both the malignant tumor and AA itself. We aimed to evaluate the efficacy of avatrombopag (AVA), a thrombopoietin receptor agonist, in patients with AA secondary to chemoradiotherapy. In this retrospective study, patients with malignant tumors who were diagnosed with AA after radiotherapy and chemotherapy and accepted AVA between September 2020 and October 2021 at Peking Union Medical College Hospital were selected. A total of 34 patients were enrolled, including 13 (38.2%) men, with a median age of 60 (20-71) years. At a median of 8 (6-18) months of follow-up, the overall response rates (ORRs) at 1, 3, and 6 months were 32.4%, 55.9%, and 58.8%, respectively, and the complete response rates (CRRs) were 5.9%, 14.7%, and 23.5%, respectively. The median time to respond was 3 (1-6) months. In total, 15.0% of patients relapsed during follow-up, but no clonal evolution was noticed. Mild side effects were observed in 17.6% of patients without drug withdrawal. At the end of follow-up, 17.6% of patients had tumors relapsed. Four patients died, three from tumor relapse and one from cerebral hemorrhage. The ORR and CRR did not correlate with eltrombopag before AVA (p > 0.05) but increased when the total exposure of AVA increased (p = 0.011), and the threshold for AVA response was a cumulative dose > 3,000 mg (p = 0.013). AVA yielded good response and tolerance in patients treated for AA secondary to chemoradiotherapy, and a higher dose may correlate with better response.

Sirolimus is effective for primary refractory/relapsed warm autoimmune haemolytic anaemia/Evans syndrome: a retrospective single-center study.

BACKGROUND: Some patients with warm autoimmune haemolytic anaemia (wAIHA) or Evans syndrome (ES) have no response to glucocorticoid or relapse. Recent studies found that sirolimus was effective in autoimmune cytopenia with a low relapse rate. METHODS: Data from patients with refractory/relapsed wAIHA and ES in Peking Union Medical College Hospital from July 2016 to May 2022 who had been treated with sirolimus for at least 6 months and followed up for at least 12 months were collected retrospectively. Baseline and follow-up clinical data were recorded and the rate of complete response (CR), partial response (PR) at different time points, adverse events, relapse, outcomes, and factors that may affect the efficacy and relapse were analyzed. RESULTS: There were 44 patients enrolled, with 9 (20.5%) males and a median age of 44 (range: 18-86) years. 37 (84.1%) patients were diagnosed as wAIHA, and 7 (15.9%) as ES. Patients were treated with sirolimus for a median of 23 (range: 6-80) months and followed up for a median of 25 (range: 12-80) months. 35 (79.5%) patients responded to sirolimus, and 25 (56.8%) patients achieved an optimal response of CR. Mucositis (11.4%), infection (9.1%), and alanine aminotransferase elevation (9.1%) were the most common adverse events. 5/35 patients (14.3%) relapsed at a median of 19 (range: 15-50) months. Patients with a higher sirolimus plasma trough concentration had a higher overall response (OR) and CR rate (p = 0.009, 0.011, respectively). At the time of enrolment, patients were divided into two subgroups that relapsed or refractory to glucocorticoid, and the former had poorer relapse-free survival (p = 0.032) than the other group. CONCLUSION: Sirolimus is effective for patients with primary refractory/relapsed wAIHA and ES, with a low relapse rate and mild side effects. Patients with a higher sirolimus plasma trough concentration had a higher OR and CR rate, and patients who relapsed to glucocorticoid treatment had poorer relapse-free survival than those who were refractory.

Comparison of eltrombopag and avatrombopag in the treatment of refractory/relapsed aplastic anemia: a single-center retrospective study in China.

Background: Eltrombopag (ELT), a thrombopoietin receptor agonist (TPO-RA), has been approved for relapsed/refractory aplastic anemia (AA). However, data on avatrombopag (AVA), another TPO-RA, are limited, and the comparisons between the two TPO-RAs are lacking. Objectives: We aimed to compare the efficacy and safety between ELT and AVA in relapsed/refractory AA patients. Design: In this retrospective study, patients with relapsed/refractory AA who had been treated with ELT (N = 45) or AVA (N = 30) alone and had compatible baseline hematological parameters were compared. Methods: Data from patients diagnosed with acquired AA were retrospectively collected. All patients were refractory/relapsed to standard immunosuppressive therapy (IST) for at least 6 months before ELT or AVA. Patients had to be treated with ELT or AVA alone for at least 6 months before evaluation if they did not respond. Baseline characteristics, overall response (OR), complete response (CR), relapse, adverse events, and factors that may affect efficacy were analyzed. Results: Of the 75 patients enrolled, 45 received ELT and 30 received AVA. Patients with AVA had a higher percentage of abnormal liver or renal function than those with ELT (p = 0.036). No significant difference was found in the OR/CR rate in the first/second/third/sixth month between the two cohorts (p > 0.05). Patients treated with AVA had a shorter median time to response than those treated with ELT (p = 0.012) and had a higher platelet level in the second month (p = 0.041). AVA had fewer adverse events than ELT (p = 0.046). Under compatible follow-up time (p = 0.463), no difference was found between the ELT and AVA cohorts in relapse (p = 1.000) or clone evolution (p = 0.637). No predictive factors for OR and CR in the sixth month were found for either ELT or AVA. Conclusion: With worse liver or renal function, AVA had a similar OR/CR rate but a shorter median time to response and fewer adverse events for patients with relapsed/refractory AA.

COVID-19 vaccination prevents a more severe course and treatment with complement inhibitors reduce worsening hemolysis during the Omicron pandemic in patients with PNH: a single-center study.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by chronic complement-mediated hemolysis. The concentrated outbreak of coronavirus disease 2019 (COVID-19) in China after 6 December 2022, provided an opportunity to observe the disease course of PNH during an active Omicron infection epidemic. PATIENTS AND METHOD: Patients diagnosed with PNH at Peking Union Medical College Hospital (PUMCH) before 6 December 2022, were followed up until 10 April 2023. Clinical data related to coronavirus infection and hemolysis were recorded. Factors influencing the infection and severity rate of Omicron, as well as hemolysis provocation, were analyzed. RESULTS: In total, 131 patients with PNH were included in this retrospective analysis; 87.8% were infected with Omicron. Among them, 15.7% met the criteria for severity, and 1 patient died (0.87%). No protective factors were identified against Omicron infections. However, patients with severe Omicron infection (n = 18) had a lower vaccination rate than those with non-severe infection (n = 97; p = 0.015). Among those infected (n = 115) with Omicron, there was a significant increase in lactate dehydrogenase (LDH) levels compared with those in the uninfected group (n = 16, p = 0.000). Patients with severe infections (n = 18) had even higher LDH increase rates than those without severe infections (n = 97; p = 0.002). 10 (37.0%) patients treated with complement inhibitors developed breakthrough hemolysis (BTH). Patients treated with complement inhibitors (n = 27) exhibited less severe hemolysis than treatment-naïve patients (n = 104; p = 0.003). CONCLUSIONS: Omicron infection exacerbates hemolytic attacks in patients with PNH. Vaccination helps mitigate the severity of Omicron infection, and using complement inhibitors reduces hemolysis exacerbation.

γδ T cells: origin and fate, subsets, diseases and immunotherapy.

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2+ γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αß T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.

Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial.

This trial compared eltrombopag (EPAG)+tacrolimus and EPAG monotherapy in patients with refractory/relapsed acquired aplastic anaemia (AA). Patients with refractory/relapsed AA were randomly assigned to receive either EPAG+tacrolimus or EPAG monotherapy at a ratio of 2:1. Patient response, safety, clonal evolution and survival were compared. In total, 114 patients were included in the analysis, with 76 patients receiving EPAG+tacrolimus and 38 receiving EPAG only. With a median follow-up of 18 (6-24) months, the overall response rate (ORR) for patients treated with EPAG+tacrolimus and EPAG alone was 38.2% vs. 31.6% (P = 0.490) at the 3rd month, 61.8% vs. 39.5% (P = 0.024) at the 6th month, 64.5% vs. 47.1% (P = 0.097) at the 12th month, and 60.5% vs. 34.2% (P = 0.008) at the last follow-up. The rate of each adverse event, overall survival curves (P = 0.635) and clonal evolution rate (P = 1.000) were comparable between the groups. A post hoc subgroup analysis showed that EPAG+tacrolimus could have advantage over EPAG monotherapy in terms of the ORR at the 6th month (P = 0.030)/last follow-up (P = 0.013) and the cumulative relapse-free survival (RFS) curves (P = 0.048) in patients <60 years old.

The Protective Effects of Bushen Daozhuo Granule on Chronic Non-bacterial Prostatitis.

Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo, BSDZG effectively reduced the prostate index. In vivo and in vitro, BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1ß, as well as the apoptosis rate. Moreover, in vivo and in vitro, BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1ß, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro. Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1ß, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.

Survival outcomes after breast-conserving surgery plus radiotherapy compared with mastectomy in breast ductal carcinoma in situ with microinvasion.

Ductal carcinoma in situ with microinvasion (DCIS-MI) is a subtype of breast cancer with a good prognosis, for which both breast conserving surgery plus radiotherapy (BCS + RT) and mastectomy are feasible surgical methods, but no clear conclusion has been made on the choice of these treatments. We used the Surveillance, Epidemiology and End Results database to extract 5432 DCIS-MI patients. Participants were divided into the BCS + RT group and the mastectomy group. We compared the overall survival (OS) and breast cancer-specific survival (BCSS) of the two groups using the Kaplan-Meier method and Cox regressions before and after propensity score matching (PSM). Before PSM, both univariate and multivariate analyses showed that BCS + RT group had significantly higher OS and BCSS compared with patients in the mastectomy group (P < 0.001). After PSM, the multivariate analysis showed that compared with mastectomy, the BCS + RT showed significantly higher OS and BCSS (HR = 0.676, 95% CI = 0.540-0.847, P < 0.001; HR = 0.565,95% CI = 0.354-0.903, P = 0.017). In addition, the subgroup analysis showed that BCS + RT is at least equivalent to mastectomy with respect to OS and BCSS in any subgroup. For patients with DCIS-MI, the prognosis of BCS + RT was superior to mastectomy.