Novel circular RNA Sestrin1 promotes chicken myoblast proliferation and differentiation via circSesn1/miR-16-5p/SESN1 pathway.

1. The development of chicken skeletal muscle is directly relevant to poultry husbandry production. Numerous studies have suggested that circular RNA play pivotal roles in muscle development. However, the functions and mechanisms of most circRNA in chicken myogenesis remain largely unknown.2. This study identified a novel circSESN1 based on existing sequencing data and examined its authenticity and subcellular localisation by enzyme digestion and RNA fluorescence in situ hybridisation. Additionally, there was a positive correlation between the expression levels of circSESN1 and the developmental stage of chicken muscle.3. Mechanistically, knockdown or overexpression of circSESN1 was performed in primary myoblasts to validate its function. The interactions between circSESN1, miR-16-5p, and the target gene sestrin 1 (SESN1) were investigated using bioinformatics analysis and a dual fluorescein reporter system. Real-time qPCR, a cell proliferation assay, and immunofluorescence staining techniques were used to investigate the promotion effect of circSESN1 on myoblast proliferation and differentiation by miR-16-5p/SESN1 pathway.4. The results demonstrated that the newly identified chicken circSESN1 directly sponges gga-miR-16-5p to regulate SESN1 gene expression, promoting myoblast proliferation and differentiation.

[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

Ultralight type I transvaginal mesh: an alternative for recurrent severe posterior vaginal prolapse.

OBJECTIVE: This study aimed to analyze the medium-term outcomes of ultralight type I mesh for postmenopausal women with recurrent severe posterior vaginal prolapse (PVP). METHODS: All participants underwent transvaginal ultralight type I mesh repair between April 2016 and April 2021 and were followed until May 2022. Pelvic Organ Prolapse Quantification System (POP-Q) staging, mesh-related complications, Patient Global Impression of Improvement (PGI-I) scale and quality of life questionnaire responses were evaluated. The primary outcome was composite surgical success rate at the last follow-up, composite success being defined as no vaginal bulge symptoms, no POP-Q point at or beyond the hymen and no re-treatment for POP. Secondary outcomes included anatomic outcomes (POP-Q score), symptomatic relief and complications. RESULTS: The median follow-up was 37.3 months. At the last follow-up, the composite success rate was 75%, and POP-Q scores for the vault and posterior wall and quality of life questionnaire scores were significantly improved (p < 0.01). The subjective satisfaction (PGI-I ≤ 2) rate was 83.3%. There were no mesh-related complications. CONCLUSIONS: Ultralight mesh can achieve good clinical outcomes and substantially improve the quality of life of patients with severe recurrent PVP in the medium term, and may thus be a viable alternative for treating this condition.

Impacts of menopause hormone therapy on mood disorders among postmenopausal women.

OBJECTIVE: This study aimed to explore the modulatory effects of menopause hormone therapy (MHT) on mood disorders among postmenopausal women. METHODS: A cross-sectional study was conducted to recruit postmenopausal women, including patients (arranged MHT for over 3 years as the medication group) and non-MHT controls. All participants were asked to respond to the Center for Epidemiological Studies Depression Scale (CES-D) and Generalized Anxiety Disorder Screener (GAD-7) questionnaires to assess their depression and anxiety status. RESULTS: A total of 230 cases from the two groups were determined based on propensity score matching analysis by matching the menopausal age and menopausal durations. We found that MHT served as a favorable modulator in the depression status of postmenopausal women. Among the four factors of the CES-D questionnaire, our data indicated that the differences between the two groups fell primarily into two aspects: depressive emotion, and somatic symptoms or retarded activities. MHT was mainly involved in improving the depression of overweight women. However, no substantial effects of MHT were observed on the regulation of anxiety. CONCLUSION: Postmenopausal women, especially the overweight population, who have experienced MHT exhibited an improved depressive status but not their anxiety condition.

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.

[A prospective study on the associations between dietary intakes of energy and macronutrients before menarche and age at menarche among girls].

Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95%CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95%CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.

Attitude and knowledge for menopause management among health professionals in mainland China.

OBJECTIVE: This study aims to understand the attitude of health-care professionals (HPs) in mainland China toward menopause management (MM) as well as the knowledge they have received regarding MM during training. METHODS: An anonymous survey recruited 3709 medical workers nationwide (including physicians, orthopedists, obstetricians and gynecologists, and general practitioners) through online surveys and on-site interviews at professional meetings. RESULTS: Of the 3709 questionnaires completed, 3426 questionnaires met the inclusion criteria. Of the participants, 1532 HPs had not received menopause management training (MMT) in nearly 1 year. Among the residents and physician assistants, 103 reported they were not familiar with MM. Satisfyingly, 98.3% of HPs considered it very important or essential to accept MM. Although most interviewees replied some correct menopausal knowledge, nearly half of them could not correctly identify the contraindications for menopause hormone therapy (MHT). Additionally, 73.1% of HPs would advise patients with premature ovarian insufficiency to receive hormone replacement therapy at least until the average age of menopause. CONCLUSION: This survey indicated that HPs have some knowledge regarding MM, but a gap remains to master the basic theory of MHT. In order to manage the growing menopausal population in China, creating more in-depth educational MMT programs for HPs is necessary.

[The association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia: a cohort study].

Objective: To examine the association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia. Methods: From January 2015 to December 2015, a total of 20 477 pregnant women were recruited by probabilistic proportional scale sampling with simple randomization in Sichuan, Yunnan and Guizhou Provinces. Basic information of pregnant women, weight gain during pregnancy and weight of newborn were collected. A multiple logistic regression model was used to assess the association between the pre-pregnancy body mass and gestational weight gain indicators with macrosomia. Results: 20 321 mother-infant were included in the final analysis. 20 321 pregnant women were (30.09±4.10) years old and delivered at (39.20±1.29) weeks, among which 12 341 (60.73%) cases were cesarean delivery. The birth weight of 20 321 infants were (3 292.26±431.67) grams, and 970 (4.77%) were macrosomia. The multiple logistic regression model showed that after adjusting for the age of women, compared to the normal weight group in the pre-pregnancy, the overweight and obesity group elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.69-2.35) and 4.05 (95%CI: 3.05-5.39), respectively. After adjusting for the age, the pre-pregnancy BMI, delivery weeks, delivery mode and infant's gender, compared to the weight-gain appropriate group, higher weight gain rate in the mid-pregnancy and excessive total gestational weight gain elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.66-2.39) and 1.80 (95%CI: 1.55-2.08), respectively. Conclusion: The overweight before pregnancy, obesity before pregnancy, the rate of weight gain in the second trimester and the high total weight gain during pregnancy could increase the risk of macrosomia.

[Effect of liraglutide in treatment of non-alcoholic fatty liver disease: mechanism of action and research advances].

Non-alcoholic fatty liver disease is a common chronic liver disease closely associated with obesity, hyperlipidemia, and diabetes. It can gradually progress to liver cirrhosis or even hepatocellular carcinoma; however, there are still no specific therapeutic agents for this disease. Liraglutide is a human glucagon-like peptide-1 analogue and has a marked effect in the treatment of type 2 diabetes. At present, many studies indicate that liraglutide also has a certain therapeutic effect on non-alcoholic fatty liver disease during the treatment of type 2 diabetes, but its mechanism of action remains unknown. This article reviews the known mechanisms of action of liraglutide in the treatment of non-alcoholic fatty liver disease.

[Blood cerebrospinal fluid barrier damage of rats induced by lead acetate or nano-lead exposure].

OBJECTIVE: To investigate the damage of blood-cerebrospinal fluid barrier (BCB) of rats induced by lead and nano-lead exposure in order to provide the basis for mechanism study of lead neurotoxicity. METHODS: 39 male rats were randomly divided into control group, lead acetate exposed group and nano-lead exposed group. Rats in lead acetate exposed group and nano-lead exposed group were given 20 mg/kg lead acetate or nano-lead by oral gavage and rats in control groups were given the same amount saline for 9 weeks.Morris maze was used to test the learning function, serum albumin and CSF albumin were determined by ELISA. Confocal laser scanning microscope was applied to detect ZO-1 and Occludin protein expression in choroid plexus, real time-PCR was used to test the expression of ZO-1 and Occludin mRNA expression. Pathological changes of choroid plexus cells were observed by the electron microscopy. RESULTS: Compared with the control group, the escape latency of rats in lead acetate or nano-lead exposure group were longer and times of across platform were less. The levels of CSF albumin and the CSF albumin index in lead acetate or nano-lead exposed rats were obviously higher, and the fluorescence intensity of ZO-1, Occludin as well as mRNA expressions were lower than those in control group(P<0.05). Compared with lead acetate exposed group, the levels of CSF albumin and the CSF albumin index in nano-lead exposure group were higher. The fluorescence intensity and mRNA expressions of ZO-1, Occludin in nano-lead exposure group were than those in lead acetate group(P<0.05). Electron microscopy revealed that lead acetate or nano-lead exposure could induce shorter microvillus of choroid plexus epithelial cells, mitochondrion destruction and partial disconnection in intracellular junctions between two adjacent epithelial cells. CONCLUSION: Lead acetate and nano-lead exposed can result in the blood-cerebrospinal fluid barrier damage, which may involve in the process of lead induced neurotoxicity. Meanwhile, nano-lead exposure can induced in more worse damage in terms of blood-results in blood-cerebrospinal fluid barrier function.

Monoenergetic positronium emission from metal-organic framework crystals.

Recently it has been discovered that positronium (Ps), after forming in metal-organic framework (MOF) crystals, is emitted into vacuum with a high efficiency and low energy that can only be explained by its propagating as delocalized Bloch states. We show that the Ps atoms are emitted from MOFs in a series of narrow energy peaks consistent with Ps at Bloch-state energy minima being emitted adiabatically into the vacuum. This implies that the Ps emission energy spectra can be directly compared with calculations to obtain detailed information about the Ps band structure in the MOF crystal. The narrow energy width of the lowest energy Ps peak from one MOF sample (2-Methylimidazole zinc salt ZIF-8) suggests it originates from a polaronic Ps surface state. Other peaks can be assigned to Ps with an effective mass of about twice that of bare Ps. Given the immense catalog of available MOF crystals, it should be possible to tune the Ps properties to make vastly improved sources with high production efficiency and a narrow energy spread, for use in fundamental physics experiments.

Anti-CII antibody as a novel indicator to assess disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects a variety of organ systems. Anti-dsDNA Abs and complement factors have been used as indicators of lupus activity for more than 50 years. A novel indicator of activation in SLE is reported in this paper. Anti-collagen type II (CII) Ab was obviously elevated in patients with SLE compared to those patients with ankylosing spondylitis (AS) and healthy controls (HCs). Anti-CII-Ab-positive patients with SLE showed significantly higher levels of serum IgG and higher titers of ANA but lower levels of C3 and C4 than controls. A positive correlation was demonstrated between anti-CII Ab and serum IgG in SLE patients (r = 0.50, p < 0.0001). The negative correlations of anti-CII Ab with C3 and C4 were observed in SLE patients (r = -0.36, p = 0.0013; r = -0.37, p = 0.0006, respectively). The reduced anti-CII Ab level was accompanied by decreased level of serum IgG and increased levels of C3 and C4 after regular treatment. Therefore, anti-CII Ab could be a novel indicator for monitoring activity of SLE.

Phylogeography and evolutionary patterns in Sporothrix spanning more than 14 000 human and animal case reports.

Pathology to vertebrate hosts has emerged repeatedly in the order Ophiostomatales. Occasional infections have been observed in Sporothrix mexicana at a low level of virulence, while the main pathogenic species cluster in a derived clade around S. schenckii s.str. In this paper, phylogeny and epidemiology of the members of this clade were investigated for 99 clinical and 36 environmental strains using four genetic loci, viz. rDNA ITS and partial CAL, TEF1, and TEF3; data are compared with amplified fragment length polymorphism (AFLP) genotyping. The four main species of the pathogenic clade were recognised. The species proved to show high degrees of endemicity, which enabled interpretation of literature data where live material or genetic information is lacking. The clade of four species comprised nine subclusters, which often had limited geographic distribution and were separate from each other in all partitions, suggesting low degrees of interbreeding between populations. In contrast, S. globosa exhibited consistent global distribution of identical AFLP types, suggesting another type of dispersal. Sporothrix brasiliensis is known to be involved in an expanding zoonosis and transmitted by cats, whereas S. globosa infections originated from putrid plant material, causing a sapronosis. Sporothrix schenckii s.str., the most variable species within the clade, also had a plant origin, with ecological similarities to that of S. globosa. A hypothesis was put forward that highly specific conditions in the plant material are required to promote the growth of Sporothrix. Fermented, self-heated plant debris may stimulate the thermodependent yeast-like invasive form of the fungus, which facilitates repeated infection of mammals.

[Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid].

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

In vitro activities of eight antifungal drugs against 106 waterborne and cutaneous exophiala species.

The in vitro activities of eight antifungal drugs against 106 clinical and environmental isolates of waterborne and cutaneous Exophiala species were tested. The MICs and minimum effective concentrations for 90% of the strains tested (n = 106) were, in increasing order, as follows: posaconazole, 0.063 µg/ml; itraconazole, 0.25 µg/ml; micafungin, 1 µg/ml; voriconazole, 2 µg/ml; isavuconazole, 4 µg/ml; caspofungin, 8 µg/ml; amphotericin B, 16 µg/ml; fluconazole, 64 µg/ml.

[A cross-sectional survey on the allocation of nursing human resources in burn centers in China].

Objective: To investigate the allocation of nursing human resources in burn centers in China. Methods: A cross-sectional survey was conducted. Using a self-designed questionnaire, a survey was carried out from January to March 2022 to investigate the January to December 2021 status of 39 burn centers in China that met the inclusion criteria based on six strategic regions and other regions, including the hospital grade and the region, the number of nurses and opening beds in the burn centers and burn intensive care units (BICUs), the age, working seniority in burn specialty, educational background, professional title, personnel employment, and turnover of nurses and training of newly recruited nurses in the burn centers. Results: This survey covered 30 provinces, municipalities, and autonomous regions in China (excluding Hong Kong Special Administrative Region, Macao Special Administrative Region, and Taiwan region of China). A total of 39 questionnaires were collected, all of which were valid. The 39 burn centers were located in 38 tertiary A hospitals and 1 tertiary B hospital, with 26 burn centers in strategic areas. The nurse/bed ratio of burn centers in the Greater Bay Area of Guangdong, Hong Kong, and Macao was the highest, while the nurse/bed ratio of burn centers in border ethnic minority area was the lowest. Except for the Chengdu-Chongqing Economic Circle, BICUs had been set up in burn centers in other regions. Among the 39 burn centers, the percentage of nurses aged 25 to 34 years was 51.21% (738/1 441), the percentage of nurses worked in burn specialty for less than 5 years was 31.16% (449/1 441), the percentage of nurses with bachelor's degree was 69.74% (1 005/1 441), and the percentage of nurses with nursing professional title was 44.14% (636/1 441), which were the highest. There were significant differences in the employment of nurses, the percentage of permanent nurses in burn centers in the collaborative development zone of Beijing-Tianjin-Hebei was 82.48% (113/137), while the percentage of permanent nurses in burn centers in important military strategic area was only 9.42% (34/361); the turnover rate of nurses was 9.03% (143/1 584), among which the turnover rate of nurses was 18.14% (80/441) in burn centers in important military strategic area. The training for newly recruited nurses in 39 burn centers was mainly based on the guidance of senior nurses and the pre-job education+specialist training. Conclusions: The burn nursing human resources in strategic areas in China are seriously insufficient and unevenly distributed, with unstable nurse team and lack of standardized specialist training. In particular, the nursing human resources in BICUs need to be equipped and supplemented urgently.

[Daratumumab maintenance after autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma].

Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Locoregional radiotherapy improves survival outcomes in de novo metastatic nasopharyngeal carcinoma treated with chemoimmunotherapy.

BACKGROUND: We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT. MATERIALS AND METHODS: We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model. RESULTS: We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51). CONCLUSIONS: Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.