Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome(MRSHSS)due to a mutation in the NFIX gene,along with a review of related literature.Both patients presented with global developmental delays,a prominent forehead,shallow eye sockets,and pectus excavatum.Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children,with parents showing wild-type at this locus.According to the guidelines of the American College of Medical Genetics and Genomics,this mutation is considered likely pathogenic and has not been previously reported in the literature.A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations.Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS.Genetic testing results are crucial for the diagnosis of this condition.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To analyze the epidemic characteristics of Cornona virus disease 2019 (COVID-19) in Wangkui County, Heilongjiang Province, and to provide a reference for optimizing epidemic prevention and control strategies.Methods:The epidemic characteristics of COVID-19 in Wangkui County, Heilongjiang Province in January 2021 were analyzed by applying the national infectious disease report system and information management system of Heilongjiang Provincial Center for Disease Control and Prevention, the public health emergency report management information system, the epidemiological investigation report of the Heilongjiang Provincial Center for Disease Control and Prevention and Suihua Municipal Certer for Disease Control and Prevention, and the epidemic information publicly released by the Health Commission of Heilongjiang Province.Results:From January 9 to February 5, 2021, 804 cases infected with Cornona virus were reported in Wangkui County, with an infection rate of 280.29/100 000. The epidemic affected 20 districts and counties in 6 cities, including Suihua, Harbin, Mudanjiang, Qiqihar, Yichun and Daqing. The sex ratio of male to female was 1.08 ∶ 1.00 (418 ∶ 386), the age ranged from 3 months to 93 years old, and the median age was 50 years old. The proportion of confirmed cases and asymptomatic infection was 1.23 ∶ 1.00 (444 ∶ 360), there were significant differences in gender, age and occupation between them ( P < 0.05). There were 314 places where the aggregation epidemic occurred, with family aggregation as the main way (300 households, 95.54%). The places with the highert average number of cases were banquets (25.75 cases/place) and grocery stores/chess and card rooms (16.00 cases/place). Conclusions:In January 2021, the epidemic of COVID-19 in Wangkui County is a typical outbreak in rural areas of North China. The main reasons for the rapid spread of the epidemic are a large number of gathering activities, frequent contact of personnel in confined spaces and other factors.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
Adaptor Proteins, Signal Transducing ; Adult ; Arteriosclerosis Obliterans/genetics* ; Autophagy ; GRB2 Adaptor Protein ; Humans ; Phosphoproteins/metabolism* ; Phosphorylation ; Protein Binding ; Signal Transduction

To reveal the processing mechanism of Chrysanthemi Flos from the changes of chemical compositions after frying and its effect on the efficacy of liver protection. Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) and ultra high performance liquid chromatography(HPLC) were used for the qualitative and quantitative researches of chemical compositions before and after Chrysanthemi Flos frying. Progenesis QI and SPSS software were used for principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), variable importance projection(VIP) analysis and t-test to identify the compositions with significant changes. Pharmacodynamics experiment was used to investigate the protective effect of crude and fried Chrysanthemi Flos on CCl_4-induced acute liver injury in mice. According to mass spectrometry data, there were 28 chemical compositions in crude and fried Chrysanthemi Flos, mainly including flavonoids and organic acids. 13 compositions such as luteolin, apigenin and luteolin glycoside were increased significantly after frying, while 7 compositions such as chlorogenic acid, luteolin-7-O-glucuronide and apigenin-7-O-glucuronide were decreased significantly after frying. Through principal component analysis, crude and fried Chrysanthemi Flos products were divided into two categories, indicating that there were internal differences in quality. The results of liver injury protection experiment in mice showed that the AST, ALT and MDA contents were significantly decreased and SOD level was increased in mice with liver injury in both the high and medium dose groups. Histopathological examination showed that crude and fried Chrysanthemi Flos can protect the liver by reducing inflammatory cell infiltration, reducing steatosis, and repairing damaged liver cells. The results of this study showed that the chemical compositions had obvious changes after frying, and both crude and fried Chrysanthemis Flos had protective effects on CCl_4-induced acute liver injury in mice. In addition, in the range of high, medium and low doses, the liver protection effect of crude and fried Chrysanthemi Flos increased with the increase of dose. The experiment results provided reference for the mechanism of fried Chrysanthemi Flos and clinical selection of processed products.
Animals ; Chromatography, High Pressure Liquid ; Chrysanthemum ; Flavonoids ; analysis ; Flowers ; chemistry ; Liver ; chemistry ; Mice

Purpose: The prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk. Materials and Methods: Clinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation.ResultTotally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort. Conclusion NPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis.

PURPOSE: The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years. MATERIALS AND METHODS: Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis–free survival (DMFS) were served as the clinical outcome. RESULTS: After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods. CONCLUSION: The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS.
Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Retrospective Studies ; Survival Rate

PURPOSE: The purpose of this study was to subdivide M1 stage nasopharyngeal carcinoma (NPC) patients with bone-only metastases for prognosis prediction while identifying the treatment effect of locoregional radiotherapy (LRRT) and metastasis radiotherapy (MRT) among patients with different risk. MATERIALS AND METHODS: From November 2006 to October 2016, a total of 226 patients with bone-only metastasic NPC were retrospectively enrolled. All patients developed distant lesions before receiving treatment. All potential prognostic factors were considered and the correlation of the M1 subdivisions with overall survival (OS) was determined by Cox regression hazards model. Kaplan–Meier curves were used to appraise survival condition and log-rank testing was used to compare the differences. RESULTS: The median follow-up time was 33.9 months (range, 3 to 126 months). According to multivariate Cox proportional hazard analysis, the number of metastatic lesions and Epstein-Barr virus (EBV) DNA status after palliative chemotherapy (PCT) were independent prognostic factors for OS. Thus, we subdivided patients into three risk groups according to these two factors. Systemic chemotherapy combined with LRRT may benefit patients in low- and intermediate-risk groups but not in the high-risk group. Further aggressive MRT based on systemic chemotherapy showed no survival benefit in any risk group. CONCLUSION: The stratification of NPC patients with bone-only metastasis based on EBV DNA after PCT and the number of metastatic lesions provided promising prognostic value and could aid clinicians in person-specific treatment.
Diagnosis ; DNA ; Drug Therapy ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Neoplasm Metastasis ; Prognosis ; Proportional Hazards Models ; Radiotherapy ; Retrospective Studies

Objective To observe the clinical efficacy of herb-partitioned fire therapy in treating stomachache due to cold-deficiency. Method Sixty patients with stomachache due to cold-deficiency were randomized into a treatment group and a control group, 30 cases each. The control group was intervened by Western and Chinese medications, based on which, the treatment group was given herb-partitioned fire therapy. The clinical efficacies of the two groups were observed, as well as the symptoms scores before and after the treatment. Result There was a significant difference in the clinical efficacy between the two groups (P<0.01). The symptoms scores dropped after the intervention in both groups, and the score in the treatment group was significantly lower than that in the control group (P<0.01). Conclusion Herb-partitioned fire therapy plus medication is effective in treating stomachache due to cold-deficiency, and it can produce a more significant efficacy than medication alone.