[Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation Patients with Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus].

OBJECTIVE: To explore the clinical characteristics and risk factors of cytomegalovirus(CMV) and Epstein-Barr virus(EBV) co-reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its influence on prognosis. METHODS: The clinical data of 222 patients who received allo-HSCT from January 2015 to December 2020 were collected, and the patients were divided into groups according to the occurrence of CMV and EBV infection. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard regression model was used to analyze the risk factors of co-reactivation of CMV and EBV. RESULTS: After allo-HSCT, there were 30 patients with co-reactivation of CMV and EBV (CMV++EBV+ group), 101 patients with CMV viremia (CMV+ group), 149 patients with EBV viremia (EBV+ group), and 28 patients with CMV and EBV inactivation (CMV-+ EBV- group). Compared with the other groups, the incidence of acute graft-versus-host disease (aGVHD) and hemorrhagic cystitis (HC) was higher in CMV++ EBV+ groups (53.3% vs 42.6%, 36.9%, 17.9%, P < 0.001; 36.7% vs 32.7%, 22.8%, 10.7%, P =0.042). The incidence of post-transplant lymphoproliferative disease (PTLD) in CMV++ EBV+ group was similar to CMV+ group and EBV+ group (3.3% vs 3.0%, 3.4%, P =0.811). Univariate and multivariate analysis showed that the persistent time of CMV and EBV after transplantation were independent risk factors for co-reactivation of CMV and EBV. Compared with the other groups, the 2-year overall survival (OS) rate and 2-year disease-free survival (DFS) rate of patients in CMV++EBV+ group were lower (46.7% vs 74.9%, 83.4%, 71.4%, P < 0.001; 46.7% vs 70.9%, 79.5%, 69.9%, P =0.002), and 2-year non-recurrence mortality (NRM) was higher (48.2% vs 22%, 13.6%, 18.7%, P <0.001). CONCLUSION: The persistent time of CMV and EBV after transplantation are independent risk factors for patients with co-reactivation of CMV and EBV. Patients with co-reactivation of CMV and EBV had lower OS and DFS rate and higher NRM, suggesting that the clinical prognosis of the patients are worse.

The RNA-binding protein RBMS3 inhibits the progression of colon cancer by regulating the stability of LIMS1 mRNA.

BACKGROUND: The RNA-binding motif single-stranded interacting protein 3 (RBMS3) is a constituent of the RNA-binding motif (RBM) protein family, which assumes a pivotal role in governing cellular biogenesis processes such as the cell cycle and apoptosis. Despite an abundance of studies elucidating RBMS3's divergent roles in the genesis and advancement of various tumors, its involvement in colon cancer remains enigmatic. METHODS: The present investigation employed data analysis from TCGA and GTEx to unveil that RBMS3 expression demonstrated a diminished presence in colon cancer tissues when juxtaposed with normal colon tissues. The effect of RBMS3 and LIM zinc finger domain 1 (LIMS1) on colon cancer was substantiated via animal models and cellular experiments. The connection between RBMS3 and LIM zinc finger domain 1 (LIMS1) was verified by molecular biology methods. RESULTS: The study conclusively ascertained that augmenting RBMS3 expression quells the proliferation, migration, and invasion of colon cancer cells. Furthermore, the inquiry unveiled a plausible mechanism through which RBMS3 impacts the expression of LIMS1 by modulating its mRNA stability. The investigation ascertained that RBMS3 inhibits the progression of colon cancer by regulating LIMS1. The inhibitory function of LIMS1 and RBMS3 is closely intertwined in colon cancer, with knocking down LIMS1 being able to rescue the inhibitory effect of RBMS3 overexpression on the functionality of colon cancer cell CONCLUSIONS: The discernments delineate RBMS3 as a novel suppressor of cancer via LIMS1, thereby bestowing fresh therapeutic possibilities and illuminating the intricacies of colon cancer.

Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The 5­year survival rate of patients diagnosed with the early stages of the disease is markedly higher than that of patients in the advanced stages. Therefore, identifying novel biomarkers and drug targets for CRC is critical for clinical practice. Zinc finger protein 169 (ZNF169) is a crucial transcription factor, and its role in CRC remains to be explored. The present study aimed to investigate the clinical relevance, function and underlying mechanisms of ZNF169 in CRC growth and proliferation. The Cancer Genome Atlas (TCGA) database was utilized to analyze the clinical relevance of ZNF169 in patients with CRC. Immunohistochemical staining was performed on tissue samples from patients with CRC to detect the expression of ZNF169. The HCT­116, HT­29 and RKO cell lines were employed for in vitro experiments. The overexpression and knockdown of ZNF169 were achieved by transfecting the cells with lentivirus and small interfering RNAs, respectively. Cell Counting Kit­8, colony formation and EdU staining assays were applied to investigate the function of ZNF169 in CRC cells. Dual luciferase activity and chromatin immunoprecipitation (ChIP)­quantitative PCR (qPCR) assays were performed to identify the regulatory effects of ZNF169 on the ankyrin repeat and zinc­finger domain­containing 1 (ANKZF1; also known as ZNF744) gene. Reverse transcription­quantitative PCR and western blot analysis were performed to measure mRNA and protein expression, respectively. The analysis of TCGA data revealed a positive correlation between ZNF169 and ANKZF1, with the overexpression of ANKZF1 being associated with a poor prognosis of patients with CRC. The experimental results demonstrated that ZNF169 was expression upregulated in CRC tissue compared with that in normal colon tissue. Gain­of­function and loss­of­function experiments revealed that ZNF169 enhanced the intensity of EdU staining, promoting the growth and proliferation of CRC cells. Furthermore, the overexpression of ZNF169 potentiated the transcriptional activity of the ANKZF1 gene, while the knockdown of ZNF169 produced the opposite results. ChIP­qPCR confirmed the interaction between ZNF169 and the promoter sequence of ANKZF1. Rescue experiments revealed that ZNF169 accelerated CRC cell growth and proliferation through the upregulation of ANKZF1. Furthermore, there was a positive correlation identified between ZNF169 and ANKZF1, and upregulation of ANKZF1 expression was associated with the poor prognosis of patients with CRC. On the whole, the present study demonstrates that ZNF169 contributes to CRC malignancy by potentiating the expression of ANKZF1. Thus, the regulation of ZNF169 and/or ANKZF1 expression may represent a viable strategy for the treatment patients with CRC with a high expression of ZNF169.

Efficacy and safety of treatment modalities for cesarean scar pregnancy: a systematic review and network meta-analysis.

OBJECTIVE: Cesarean scar pregnancy may lead to varying degrees of complications. There are many treatment methods for it, but there are no unified or recognized treatment strategies. This systematic review and network meta-analysis aimed to observe the efficacy and safety of treatment modalities for patients with cesarean scar pregnancy. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 31, 2024. In addition, relevant reviews and meta-analyses were manually searched for additional references. STUDY ELIGIBILITY CRITERIA: Our study incorporated head-to-head trials involving a minimum of 10 women diagnosed with cesarean scar pregnancy through ultrasound imaging or magnetic resonance imaging, encompassing a detailed depiction of primary interventions and any supplementary measures. Trials with a Newcastle-Ottawa scale score <4 were excluded because of their low quality. METHODS: We conducted a random-effects network meta-analysis and review for cesarean scar pregnancy. Group-level data on treatment efficacy and safety, reproductive outcomes, study design, and demographic characteristics were extracted following a predefined protocol. The quality of studies was assessed using the Cochrane risk-of-bias tools for randomized controlled trials and the Newcastle‒Ottawa scale for cohort studies and case series. The main outcomes were efficacy (initial treatment success) and safety (complications), of which summary odds ratios and the surface under the cumulative ranking curve using pairwise and network meta-analysis with random effects. RESULTS: Seventy-three trials (7 randomized controlled trials) assessing a total of 8369 women and 17 treatment modalities were included. Network meta-analyses were rooted in data from 73 trials that reported success rates and 55 trials that reported complications. The findings indicate that laparoscopy, transvaginal resection, hysteroscopic curettage, and high-intensity focused ultrasound combined with suction curettage demonstrated the highest cure rates, as evidenced by surface under the cumulative ranking curve rankings of 91.2, 88.2, 86.9, and 75.3, respectively. When compared with suction curettage, the odds ratios (95% confidence intervals) for efficacy were as follows: 6.76 (1.99-23.01) for laparoscopy, 5.92 (1.47-23.78) for transvaginal resection, 5.00 (1.99-23.78) for hysteroscopic curettage, and 3.27 (1.08-9.89) for high-intensity focused ultrasound combined with suction curettage. Complications were more likely to occur after receiving uterine artery chemoembolization, suction curettage, methotrexate+hysteroscopic curettage, and systemic methotrexate; hysteroscopic curettage, high-intensity focused ultrasound combined with suction curettage, and Lap were safer than the other options derived from finite evidence; and the confidence intervals of all the data were wide. CONCLUSION: Our findings indicate that laparoscopy, transvaginal resection, hysteroscopic curettage, and high-intensity focused ultrasound combined with suction curettage procedures exhibit superior efficacy with reduced complications. The utilization of methotrexate (both locally guided injection and systemic administration) as a standalone medical treatment is not recommended.

A multi-variable predictive warning model for cervical cancer using clinical and SNPs data.

Introduction: Cervical cancer is the fourth most common cancer among female worldwide. Early detection and intervention are essential. This study aims to construct an early predictive warning model for cervical cancer and precancerous lesions utilizing clinical data and simple nucleotide polymorphisms (SNPs). Methods: Clinical data and germline SNPs were collected from 472 participants. Univariate logistic regression, least absolute shrinkage selection operator (LASSO), and stepwise regression were performed to screen variables. Logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), extreme gradient boosting(XGBoost) and neural network(NN) were applied to establish models. The receiver operating characteristic (ROC) curve was used to compare the models' efficiencies. The performance of models was validated using decision curve analysis (DCA). Results: The LR model, which included 6 SNPs and 2 clinical variables as independent risk factors for cervical carcinogenesis, was ultimately chosen as the most optimal model. The DCA showed that the LR model had a good clinical application. Discussion: The predictive model effectively foresees cervical cancer risk using clinical and SNP data, aiding in planning timely interventions. It provides a transparent tool for refining clinical decisions in cervical cancer management.

Synaptic mechanisms underlying the elevated sympathetic outflow in fructose-induced hypertension.

Metabolic syndrome is associated with cardiovascular dysfunction, including elevated sympathetic outflow. However, the underlying brain mechanisms are unclear. The nucleus tractus solitarius (NTS) critically regulates autonomic reflexes related to cardiovascular function and contains neurons projecting to the caudal ventrolateral medulla (CVLM). Nitric oxide (NO) is a diffusible free-radical messenger in the vascular, immune, and nervous systems. In this study, we determine if NO in the NTS is involved in the synaptic plasticity underlying the elevated sympathetic outflow in fructose-induced hypertension. We retrogradely labeled CVLM-projecting NTS neurons through the injection of FluoSpheres into the CVLM in a fructose-fed rat model to determine the cellular mechanism involved in increased sympathetic outflow. Fructose feeding increased the blood pressure and glucose levels, which represent metabolic syndrome. We found that fructose feeding reduces the NO precursor L-arginine-induced increase in the firing activity of CVLM-projecting NTS neurons. Furthermore, fructose feeding reduces the L-arginine-induced increase in presynaptic spontaneous glutamatergic synaptic inputs to NTS neurons, while NO donor DEA/NO produces an increase in glutamatergic synaptic inputs in fructose-fed rats similar to that in vehicle-treated rats. In addition, fructose feeding reduces the NO-induced depressor response and sympathoinhibition. These data suggested that fructose feeding reduced NO production and, thus, the subsequent NO-induced glutamate releases in the NTS and depressor response. The findings of this study provide new insights into the central mechanisms involved in the neural control of cardiovascular and autonomic functions in the NTS in metabolic syndrome.

Recruitment of ubiquitin E2 enzymes is determined jointly by the U-box domains and substrates of E3 ligases.

Ubiquitination is a cascade reaction involving E1, E2, and E3 enzymes. The orthogonal ubiquitin transfer (OUT) method has been previously established to identify potential substrates of E3 ligases. In this study, we verified the ubiquitination of five substrates mediated by the E3 ligases CHIP and E4B. To further explore the activity of U-box domains of E3 ligases, two mutants with the U-box domains interchanged between CHIP and E4B were generated. They exhibited a significantly reduced ubiquitination ability. Additionally, different E3s recruited similar E2 ubiquitin-conjugating enzymes when ubiquitinating the same substrates, highlighting that U-box domains determined the E2 recruitment, while the substrate determined the E2 selectivity. This study reveals the influence of substrates and U-box domains on E2 recruitment, providing a novel perspective on the function of U-box domains of E3 ligases.

The prognostic significance of POD24 in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes.

The safety and efficacy of sabatolimab, a novel immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), was assessed in combination with hypomethylating agents (HMAs) in patients with HMA-naive revised International Prognostic System Score (IPSS-R) high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) or chronic myelomonocytic leukemia (CMML). Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

Middle Ear Meningioma With Recurrence Secretory Otitis Media.

Middle ear meningiomas (MEMs) are rare tumors that can present with nonspecific symptoms, posing challenges in diagnosis and management. This case report focuses on a middle-aged female patient who was misdiagnosed with secretory otitis media for 5 years. However, further evaluation through computed tomography imaging and subsequent pathologic biopsy revealed the presence of a MEM. The patient underwent surgical and gamma knife resection of the tumor and follow-up examination after 1 year showed no signs of recurrence. This case report highlights the importance of considering meningiomas in the differential diagnosis of middle ear pathologies and the need for careful preoperative planning for optimal outcomes. Overall, this case demonstrates that correct diagnosis and appropriate treatment can lead to successful management of MEMs.

OS and DFS are affected by different diagnostic methods and hysterectomy procedures in endometrial cancer patients: A single-center retrospective study.

PURPOSE: We aimed to evaluate whether hysteroscopy increases the risk of intraperitoneal dissemination or worsens the prognosis of endometrial carcinoma (EC) patients and whether radical hysterectomy (RH) improves overall survival (OS) or disease-free survival (DFS) in patients with stage II to III EC and to investigate the effects of different procedures for identifying EC and the effects of different surgical methods on the OS and DFS of endometrial cancer patients. METHODS: Four hundred sixty-five women with EC were included in this retrospective study. Log-rank tests and Kaplan-Meier analysis were used for the outcome comparisons of the effects of the EC diagnostic method and different hysterectomy procedures. A Cox proportional hazards model was used for univariate regression analysis. RESULTS: Among the three procedures for diagnosing EC (diagnostic curettage, hysteroscopy, and hysterectomy), the incidences of fallopian tube and ovarian invasion were not significantly different (p = 0.506 and 0.066, respectively). The diagnostic methods for EC had no significant effect on OS (p = 0.577) or DFS (p = 0.294). In addition, type II RH and type III RH did not improve the prognosis of patients with FIGO stage II and III disease (log-rank p = 0.914 and 0.810 for OS; log-rank p = 0.707 and 0.771 for DFS, respectively). CONCLUSION: Based on the current study evidence, the use of diagnostic hysteroscopy procedures is safe and does not increase the risk of fallopian tube and ovarian invasion of intraperitoneal dissemination or worsen the prognosis of EC patients. Type II and type III RH did not demonstrate a benefit for stage II-III EC patients.

Co-doping of Ho-Yb ion pairs modulating the up-conversion luminescence properties of fluoride phosphors under 1550 nm excitation.

In this study, up-conversion fluoride phosphors NaY1-x-y-m-nMxF4:Er3+y,Ho3+m,Yb3+n (M = Lu3+/Gd3+) were synthesized by a low-temperature combustion method. The optimal ionic ratios in the matrix lattice were also determined by a controlled variable method. It was confirmed that doping a small amount of Ho3+ ions and Yb3+ ions in the Er-doped sample matrix lattice can form a mutual sensitizer and a transient energy capture center to enhance the sample's up-conversion luminescence under excitation at the 1550 nm band, respectively. It was also found that the lanthanide ion introduced can modulate the red-to-green ratio of the up-conversion luminescence of the sample. The phase composition and morphology of phosphors were investigated using X-ray diffraction and scanning electron microscopy. The up-conversion luminescence mechanism of Er-Ho-Yb tri-doped samples excited at the 1550 nm band was also investigated. This work presents a novel approach for improving up-conversion luminescence with high color-purity phosphors for display lighting applications when excited at 1550 nm.

Prognostic value of prelymphodepletion absolute lymphocyte counts in relapsed/refractory diffuse large B-cell lymphoma patients treated with chimeric antigen receptor T cells.

Introduction: Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented efficacy recently. However, the factors related to responses and durable remission are elusive. This study was to investigate the impact of pre-lymphodepletion (pre-LD) absolute lymphocyte count (ALC) on CAR T cell therapy outcomes. Methods: We conducted a retrospective study of 84 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who underwent CAR T cell treatment at the Affiliated Hospital of Xuzhou Medical University between March 1,2016 and December 31, 2021. The enrolled patients were divided into high group and low group according to the optimal cutoff value of pre-LD ALC. The Kaplan-Meier analyses was used to calculate survival curves. The Cox proportional hazards model was used for univariate and multivariate analysis to assess the prognostic factors. Results: The ROC showed that the optimal cutoff value of pre-LD ALC was 1.05 x 109/L. The overall response (defined as partial response or complete response) rate was significantly higher in patients with a high pre-LD ALC (75% versus 52.08%; P=0.032). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those having a high pre-LD ALC (median OS, 9.6 months versus 45.17 months [P=0.008]; median PFS, 4.07 months versus 45.17 months [P= 0.030]). Meanwhile, low pre-LD ALC is an independent risk factor for PFS and OS. Discussion: The data suggested that pre-LD ALC may serve as a helpful indicator to predict the outcomes of CAR T cell therapy in patients with R/R DLBCL.

Sabatolimab (MBG453) model-informed drug development for dose selection in patients with myelodysplastic syndrome/acute myeloid leukemia and solid tumors.

Sabatolimab is a novel immunotherapy with immuno-myeloid activity that targets T-cell immunoglobulin domain and mucin domain-3 (TIM-3) on immune cells and leukemic blasts. It is being evaluated for the treatment of myeloid malignancies in the STIMULUS clinical trial program. The objective of this analysis was to support the sabatolimab dose-regimen selection in hematologic malignancies. A population pharmacokinetic (PopPK) model was fit to patients with solid tumors and hematologic malignancies, which included acute myeloid leukemia, myelodysplastic syndrome (including intermediate-, high-, and very high-risk per Revised International Prognostic Scoring System), and chronic myelomonocytic leukemia. The PopPK model, together with a predictive model of sabatolimab distribution to the bone marrow and binding to TIM-3 was used to predict membrane-bound TIM-3 bone marrow occupancy. In addition, the total soluble TIM-3 (sTIM-3) kinetics and the pharmacokinetic (PK) exposure-response relationship in patients with hematologic malignancies were examined. At intravenous doses above 240 mg Q2w and 800 mg Q4w, we observed linear PK, a plateau in the accumulation of total sTIM-3, and a flat exposure-response relationship for both safety and efficacy. In addition, the model predicted membrane-bound TIM-3 occupancy in the bone marrow was above 95% in over 95% of patients. Therefore, these results support the selection of the 400 mg Q2w and 800 mg Q4w dosing regimens for the STIMULUS clinical trial program.

Port Site Metastasis After Minimally Invasive Surgery in Gynecologic Malignancies: Two Case Reports and a Review of the Literature.

Port site metastasis (PSM) is considered an uncommon and rare complication in gynecologic malignancies with unclear treatment recommendations or guidelines. Thus, we report the treatment strategies and outcomes of two cases of PSMs following gynecologic malignancies and a review of the literature to provide much information about the most frequent sites of PSMs and the incidence of PSMs in different gynecological tumors. A 57-year-old woman underwent laparoscopic radical surgery for right ovarian serous carcinoma in June 2016 followed by postoperative chemotherapy. Because PSMs were present near the port site of the bilateral iliac fossa, the tumors were completely removed on August 4, 2020, and the patient received chemotherapy. She has shown no signs of relapse. During the same period, a 39-year-old woman underwent laparoscopic type II radical hysterectomy for endometrial adenocarcinoma involving the endometrium and cervix on May 4, 2014, without adjuvant treatment. In July 2020, a subcutaneous mass under her abdominal incision was removed, and chemotherapy plus radiotherapy was administered. Metastasis was found in the left lung in September 2022, but there was no abnormality in the abdominal incision. We showed the two cases of PSMs, reviewed articles to provide some new insights about the incidences of PSMs in the gynecologic tumors, and discussed the proper preventive strategies.

Postoperative Adjuvant Treatment in Women with Stage I Endometrial Cancer: A Retrospective Study.

Objective: To evaluate whether postoperative adjuvant treatment is beneficial for patient survival after surgery for early stage endometrial cancer (EC). We analyzed the outcomes of patients treated with radiotherapy, chemotherapy, or progestagen combined with other adjuvant treatments. Methods: We analyzed the outcomes of patients treated with radiotherapy alone, chemotherapy alone, or progestagen treatment with other adjuvant treatments. Women without any adjuvant treatment after operation were used as controls. We retrospectively examined disease-free survival (DFS), overall survival (OS), and high-risk factors that affected the survival status of all patients who received different postoperative adjuvant therapies. Results: In all 192 patients, the total relapse and mortality rates were 5.57% and 1.68%, respectively. Fourteen patients (7.29%) developed isolated local recurrence, and 2 patients died (1.04%) of recurrence during the follow-up period. The 5-year DFS and OS rates of all patients were 95.83% and 93.75%, respectively. No significant differences were observed in the 5-year DFS, 5-year OS, OS, or DFS among the four groups of patients with FIGO stage I endometrial cancer (P=0.9849, 0.7430, 0.9754, and 0.4534, respectively). The differences in the log-rank test results of the estimates of the 5-year DFS, 5-year OS, DFS, and OS of patients with different disease stages and different ages were all significant, but no differences were observed in these parameters among patients with varying degrees of differentiation. Histologic grade, CA125 level, ER and PR status, and adjuvant therapy had no significant effect on the DFS and OS of all patients according to univariate and multivariate regression analyses, but a significant effect on DFS and OS was found when the patients were stratified by age. Conclusion: This retrospective study showed that adjuvant therapy after surgery was not significantly associated with improved DFS or OS in patients with early stage endometrial cancer. However, FIGO stage and age affected the survival of patients with stage I endometrial cancer.

Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma.

BACKGROUND AIMS: Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy. METHODS: Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy. RESULTS: Both groups of patients had similar duration of grade 3-4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 µg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell-treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non-G-CSF group. CONCLUSIONS: Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy.

Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase â ¡ Trial.

PURPOSE: G protein-coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM. METHODS: This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients. RESULTS: From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache). CONCLUSION: Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.

3D carbonized grooved straw with efficient evaporation and salt resistance for solar steam generation.

Solar steam generation (SSG) is considered an effective solution to the global shortage of freshwater resources. To solve the practical application challenges of SSG in remote outdoor environments where electricity is scarce, it is of great importance to developing new solar evaporators. In this study, a three-dimensional (3D) biochar solar evaporator based on carbonized grooved straw was prepared from agricultural waste corn straw, which had high solar energy conversion efficiency and excellent salt resistance. The existence of grooves increases the surface area to absorb more sunlight and makes the light multilevel reflection improve the evaporation rate. The excellent light absorption, super hydrophilic, and heat shielding properties of 3D carbonized grooved straw resulted in a good evaporation rate (1.57 kg⋅m-2·h-1) and energy efficiency (85.9%) under 1 sun irradiation. The 3D grooved biochar solar distiller also demonstrated efficient formation evaporation performance and excellent salt resistance in practical applications in seawater desalination and surface water purification. The 3D grooved biochar solar distiller prepared from agricultural waste has the advantages of being economical and environmentally friendly, with good application prospects.

A Rare Case of Deceptive Maxillary Ameloblastoma.

Ameloblastoma (AM) is a rare epithelium-derived odontogenic tumor, mostly involving the mandible and less often the maxilla. Most AMs are benign and characterized by indolence and local invasiveness, with a high recurrence rate. Herein, we present a case of maxillary AM in a 42-year-old female suffering from left nasal congestion and facial swelling for almost one month after endoscopic surgery at a local hospital. The mass was completely resected by a transnasal functional endoscopic sinus surgery based on radiographic examination. Subsequently, postsurgical histopathological examinations were conducted, and she was diagnosed with a plexiform AM pattern. Immunohistochemical staining revealed that the tumor was positive for PCK, P63, CK5/6, and CK14 but negative for S100, ER, and Ki67. Based on these findings, the patient was diagnosed with maxillary AM.