Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Humans ; Male ; Adult ; Female ; Xanthomatosis, Cerebrotendinous/pathology* ; Pedigree ; Cholestanetriol 26-Monooxygenase/genetics* ; Mutation ; Ataxia

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective:To explore the potential of thrombus-targeted nanoprobes for ultrasound/near-infrared bimodal imaging and their synergistic therapeutic effects on thrombosis in vitro.Methods:Nanoprobes loaded with arginine-glycine-aspartate peptide (RGD), perfluoropentane (PFP) and indocyanine green (ICG) were prepared by ultrasonic vibration and carbodiimide method with mesoporous silica nanoparticle (MSN) as the carrier. The probe morphology was observed by scanning and transmission electron microscopy. The loading of RGD and ICG was detected by Bicinchoninic Acid Assay (BCA) and UV-Visible-NIR spectroscopy respectively. The imaging performance and photothermal response of the nanoprobe under near infrared light (NIR) irradiation were studied in vitro. Its biological safety was tested by cytotoxicity test and hemolysis test. The phase transformation was studied under ultrasound and NIR irradiation. The nanoprobe was incubated with fresh arterial thrombus, and its target-seeking ability was observed by frozen section. Ultrasound and NIR irradiation were used to evaluate its thrombolytic ability by the weight changes of thrombus before and after irradiation.Results:The prepared nanoprobe had regular morphology and uniform size. The particle diameter was (156.83±5.05)nm, and the surface potential was (11.47±0.25)mV. The RGD coupling rate was (77.67±4.50)%, which could mediate the targeting of nanoprobe to fresh extracorporeal arterial thrombus. UV-Visible-NIR spectroscopy confirmed the successful loading of ICG, and its encapsulation rate was (80.47±0.05)%. After ultrasound and NIR irradiation, the nanoprobe could undergo acoustically induced phase transition, thermally induced phase transition and enhance the ultrasonic development effect. With the increase of the concentration of the nanoprobe solution, the NIR signal gradually increased, and the temperature rose in a concentration-dependent and intensity-dependent manner after NIR irradiation. The cytotoxicity test and hemolysis test showed that the nanoprobe had good biological safety, and it could play a thrombolytic role under the combined irradiation of ultrasound and NIR, and the weight of thrombus was significantly reduced after the treatment ( P<0.01). Conclusions:In this study, the nanoprobe (RGD/ICG/PFP@MSN) were successfully prepared possesses excellent dual mode imaging capabilities of ultrasound and NIR, excellent phase transition ability and photothermal conversion efficiency, as well as efficient targeted penetration and therapeutic effects against thrombosis. This study provides strong in vitro experimental evidence and new strategies for the integration of diagnosis and treatment of thrombotic diseases under the cooperation of ultrasound and NIR.

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:To investigate the association of preoperative neutrophil-lymphocyte ratio combined with platelet-to-lymphocyte ratio (NLR-PLR) score with clinicopathological parameters and prognosis in patients with colorectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 178 patients with colorectal cancer who were admitted to the First Affiliated Hospital of China Medical University from January 2013 to December 2014 were collected. There were 101 males and 77 females, aged from 21 to 90 years, with an average age of 63 years. All patients underwent radical resection of colorectal cancer. Observation indicators: (1) cutoffs of NLR and PLR and correlation between them; (2) association between preoperative NLR-PLR score and clinicopathological characteristics of patients with colorectal cancer; (3) follow-up and survival; (4) analysis of the risk factors for prognosis of patients with colorectal cancer. Follow-up was performed once every 3 months using outpatient examination or telephone interview including tumor markers, computed tomography and enteroscopy to detect postoperative survival of patients up to June 2017. Overall survival time was defined as the date of surgery to the date of the last valid follow-up or the date of death. Measurement data with skewed distribution were expressed as M (range). Count data were expressed as absolute numbers, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was performed using the Mann-Whitney U test. Kaplan-Meier method was used to draw survival curve, and Log-rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) Cutoffs of NLR and PLR and correlation between them. Receiver working characteristics of NLR and PLR showed that the NLR had a cutoff of 2.7 [area under curve (AUC)=0.739, 95% confidence interval ( CI): 0.638-0.841, P<0.05] and PLR had a cutoff of 246 (AUC=0.640, 95% CI: 0.521-0.758, P<0.05). There was a correlation between NLR and PLR ( r=0.712, P<0.05). (2) Association between preoperative NLR-PLR score and clinicopathological characteristics of patients with colorectal cancer. Results of preoperative NLR-PLR score showed that the NLR-PLR score was 0, 1, and 2 in 99, 52, and 27 patients, respectively. There were significant differences in tumor diameter, degree of tumor invasion, TNM staging, Dukes staging, and distant metastasis between patients with different preoperative NLR-PLR scores ( χ2=11.294, 10.816, 9.802, 9.525, 8.759, P<0.05). (3) Follow-up and survival: 178 patients were followed up for 1-53 months, with a median follow-up time of 37 months. The average survival time was 37 months for all the 178 patients, 50 months for 99 patients with NLR-PLR score of 0, 44 months for 52 patients with NLR-PLR score of 1, and 35 months for 27 patients with NLR-PLR score of 2. There was a significant difference in survival time between patients with NLR-PLR score of 0 and patients with NLR-PLR score of 1 ( χ2=6.388, P<0.05), between patients with NLR-PLR score of 0 and patients with NLR-PLR score of 2 ( χ2=26.388, P<0.05), between patients with NLR-PLR score of 1 and patients with NLR-PLR score of 2 ( χ2=5.350, P<0.05). (4) Analysis of the risk factors for prognosis of patients with colorectal cancer. Results of univariate analysis showed that degree of tumor invasion, TNM staging, Dukes staging, distant metastasis, NLR-PLR score, and platelet-NLR score were related factors for prognosis of patients with colorectal cancer [ hazard ratio ( HR)=2.439, 2.472, 2.221, 9.020, 2.671, 2.099, 95% CI: 1.443-4.124, 1.413-4.323, 1.282-3.849, 4.449-18.082, 1.742-4.097, 1.339-3.290, P<0.05]. Results of multivariate analysis showed that degree of tumor invasion, distant metastasis, and NLR-PLR score were independent factors for prognosis of patients with colorectal cancer ( HR=2.045, 5.641, 2.271, 95% CI: 1.051-3.979, 2.590-12.288, 1.185-4.354, P<0.05). Conclusions:The preoperative NLR-PLR score is associated with tumor diameter, degree of tumor invasion, TNM staging, Dukes staging, and distant metastasis in patients with colorectal cancer. Patients with higher score have larger tumor diameter, higher degree of tumor invasion, higher stage, and easier distant metastasis. Preoperative NLR-PLR score can effectively evaluate the prognosis of patients with colorectal cancer. Patients with higher NLR-PLR score have shorter survival time. The NLR-PLR score is an independent influencing factor for prognosis of patients with colorectal cancer.

Objective:To investigate the infection rate of Paris polyphylla var. yunnanensis at different periods，the changes of mineral nutrients in rhizosphere soil and the correlation among the factors under different arbuscular mycorrhizal （AM） fungi conditions. Method:28 kinds of AM fungi were inoculated into the seedlings of P. polyphylla var. yunnanensis by single factor pot experiment. The samples were collected in August （fruit ripening period） and November （senescence period） to analyze the infection rate and the physical and chemical properties of rhizosphere soil. Result:The mycorrhizal infection rate of each treatment group was 75%-100% in the fruit ripening period and senescence period. The contents of easily extracted glomalin and total glomalin in rhizosphere soil increased to different degrees in these two periods as compared with CK group， the pH of rhizosphere soil in the two treatment groups showed an increasing trend， the content of organic matter in rhizosphere soil decreased significantly in the fruit ripening period in all the treatment groups，and the organic matter in rhizosphere soil in the senescence period showed no significant differences. The total N and K contents in rhizosphere soil decreased in both periods， and the other physical and chemical properties of rhizosphere soil increased or decreased without significant change regularity. Correlation analysis showed that the infection rate was correlated with the physical and chemical properties of rhizosphere soil to a certain degree. Conclusion:Inoculation of AM fungi can affect the physical and chemical properties of rhizosphere soil of P. polyphylla var. yunnanensis to some extent，and provide reference value for the application of AM fungi in the cultivation of traditional Chinese medicine.