Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Objective:To investigate the biomechanical properties of cannulated screws fixation in a configuration of "axial compression and lateral buttress" in the treatment of Pauwels type Ⅱ femoral neck fractures.Methods:Ten specimens of Sawbones artificial femur were first made into models of type Ⅱ femoral neck fracture with a Pauwells angle of 50° and then randomized into 2 equal groups ( n=5). The specimens in the experimental group were subjected to fixation with cannulated screws in a configuration of "axial compression and lateral buttress" in which the axial screw was 8.5 mm in diameter and the lateral screw 6.5 mm in diameter. The specimens in the control group were subjected to conventional fixation with cannulated screws in a configuration of "inverted triangle and parallel compression" in which the 3 screws was 7.3 mm in diameter. Finally, the specimens were placed onto a biomechanical testing machine to determine the parameters of static axial stiffness, displacement under 60 to 600 N load for 5,000 cycles, ultimate load and ultimate stiffness in turn. The 2 groups were compared to find out their differences. Results:The static axial stiffness was (1,492.00 ± 87.86) N/mm, significantly higher than that in the control group [(1,200.22 ± 228.06) N/mm] ( P<0.05). There was no significant difference between the 2 groups in the cyclic load displacement [(0.44 ± 0.01) mm versus (0.57 ± 0.17) mm] ( P>0.05), but the experimental group showed a lower trend. The ultimate load and ultimate stiffness were (4,292.61 ± 804.29) N and (1,623.55 ± 180.94) N/mm in the experimental group and (4,383.64 ± 1,423.24) N and (1,433.77 ± 289.93) N/mm in the control group, showing no significant difference between the 2 groups ( P>0.05). Conclusion:In the treatment of Pauwels type Ⅱ femoral neck fractures, fixation with cannulated screws in a configuration of "axial compression and lateral buttress" may exhibit better biomechanical properties than that in a conventional configuration of "inverted triangle" .

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated Rdh13 knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on liver injury induced by carbon tetrachloride (CCl). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the Rdh13 mice displayed an attenuated response to CCl-induced liver injury. Their livers also exhibited less histological changes and contained lower levels of liver-related metabolism enzymes compared with the livers of wild-type (WT) mice. Furthermore, the Rdh13 mice had Rdh13 deficiency and thus their liver cells were protected from apoptosis, and the quantity of their proliferative cells became lower than that in WTafter CCl exposure. The ablation of Rdh13 gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (Cyp2e1) in the liver, especially after CCl treatment for 48 h. These data suggested that the alleviated liver damage induced by CCl in Rdh13 mice was caused by Cyp2e1 enzymes, which promoted reductive CCl metabolism by altering the status of thyroxine metabolism. This result further implicated Rdh13 as a potential drug target in preventing chemically induced liver injury.
Alcohol Oxidoreductases ; deficiency ; genetics ; Animals ; Carbon Tetrachloride Poisoning ; enzymology ; Chemical and Drug Induced Liver Injury ; enzymology ; pathology ; Cytochrome P-450 CYP2E1 ; metabolism ; Female ; Immunohistochemistry ; Liver ; drug effects ; enzymology ; pathology ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Proteins ; metabolism ; Transcription Factors ; metabolism

Objective: To investigate the effect of licorice on radio-sensitization of nasopharyngeal carcinoma CNE-2 cells and its mechanism. Methods: The radio-resistant nasopharyngeal carcinoma cell line (CNE-2-RR) was constructed and cultured in vitro. MTT assay was used to detect the effect of different concentrations of licorice on the proliferation activity of nasopharyngeal carcinoma cells. The changes of autophagosome in CNE-2-RR cells after licorice treatment were observed by transmission electron microscopy (TEM). Western blotting was used to detect the effect of licorice on the level of autophagy protein in CNE-2-RR cells. Single cell gel electrophoresis (comet assay) was used to detect the DNAdamage and repair of different groups of CNE-2-RR cells. Flow cytometry was used to detect the apoptosis rate of CNE-2-RR cell line. Results: Low-radiation resistant CNE-2-RR cell line was successfully constructed; MTT assay showed that 20 mmol/L licorice exhibited highest inhibition on CNE-2-RR cells (58.86 ± 5.02)%. Transmission electron microscopy showed increased autophagicbody and abnormal mitochondria and nuclei morphology in CNE-2-RR cells after treatment. Western blotting showed that autophagic protein LC3-II level was increased and LC3-I level was decreased in CNE-2-RR cells (P < 0.05). The results of single cell gel electrophoresis showed that the length of comet tail distance of CNE-2-RR cells after licorice treatment was higher than that of the control group (P<0.05), indicating weakened repair ability of DNA damage. Conclusion: Licorice enhances the radio-sensitivity of CNE-2-RR cells by influencing autophagy and DNArepair ability.

Objective: To observe the infection status and the distribution of the gene subtypes of human papillomavirus (HPV) in Huzhou. Methods: Cervical exfoliated cells were collected from the women who attended the physical examination and the cervical HPV examination from June 2017 to December 2017 in Huzhou Maternal and Child Health-Care hospital. A total of 2 830 women were tested for 21 HPV genotypes (including HPV-16, 18, 31, 59, 66, 53, 33, 58, 45, 56, 52, 35, 68, 51, 39, 82, 26, 73, 6, 11, 81), using real-time polymerase chain reaction (RT-PCR), investigated the infection status and subtype distribution. Results: Among the 2 830 women, 269 were positive for HPV, the total infection rate was 9.51% (269/2 830). The infection rate of single gene and double gene was 86.99% (234/269) and 11.90% (32/269), respectively. The infection rate of high-risk subtypes was 9.11% among the detected women (258/2 830), accounting for 83.77% of HPV gene detections (258/308). The HPV-58, 16, 52 were the most commonly found gene subtypes among the high-risk HPV. The rate of HPV infection and high-risk subtypes of HPV infection in women was the highest in the 56-60 year old group, and the lowest in the 31-35 year old group. In different age groups, the difference in high-risk HPV infection rate was statistically significant, the total infection rate had no statistical significance. Conclusions In Huzhou area, the HPV infection rate of women found through normal physical examination was 9.51%, the high risk type was 58, 16 and 52, and the 56-60 year old group was the high incidence group. This study provides the HPV infection status and HPV gene subtype distribution characteristics in women in Huzhou, which has important guiding value for the vaccine development and application, and for prevention of HPV infection.

OBJECTIVETo assess the value of whole-genome amplification (WGA) and next generation sequencing (NGS) for the pre-implantation screening of discarded embryos.

METHODSIn total 476 discarded embryos were collected. After continued culture, 23 high-quality blastocysts were obtained. Blastocysts graded as 4BC or above based on Gardner classification were subjected for blastula biopsy. Five to ten nourish ectoderm cells were hatched with a biopsy needle. Following WGA and NGS, deletion and/or duplication of chromosomal fragments and numerical chromosomal aberrations were analyzed.

RESULTSIn total 148 trophoblast cells were obtained from the 23 blastocysts. Following WGA, 60 amplification products were selected for NGS. The results showed that there were 39 abnormal chromosomes derived from 14 blastocysts, which gave an abnormal rate of blastocyst of 60.87% (14/23).

CONCLUSIONWGA combined with NGS can enable pre-implantation genetic screening for discarded embryos, which may improve the efficacy of in vitro fertilization as well as reduce the risk for birth defects.