OBJECTIVE To observe the expressions of microribonucleic acid(miR)-155,miR-141,interleukin(IL)-22 and IL-17 in peripheral blood of the chronic renal failure(CRF)and hemodialysis(HD)patients compli-cated with hospital-associated infections and analyze the clinical treatment outcomes.METHODS A total of 561 CRF patients who underwent HD in Wuhan First Hospital from Jun.2022 to Jun.2023 were enrolled in the study and were divided into the infection group with 182 cases and the non-infection group with 379 cases according to the status of hospital-associated infections.The patients of the infection group were divided into the survival group with 138 cases and the death group with 44 cases according to the clinical therapeutic outcomes of a 6-month fol-low-up.The distribution of pathogens isolated from the CRF HD patients with hospital-associated infections was analyzed,the clinical data were compared between the infection group and the non-infection group;the levels of serum miR-155,miR-141,IL-22 and IL-17 were observed and compared among the groups.The values of the se-rologic markers in prediction of the clinical therapeutic outcomes of the CRF HD patients with hospital-associat-ed infections were analyzed by receiver operating characteristic(ROC)curves.RESULTS The proportions of pa-tients with no less than 1 year of hemodialysis,femoral venous catheter indwelling and long-term catheter indwell-ing were higher in the infection group than those in the non-infection group(P＜0.05).Totally 202 strains of pathogens were isolated from the infection group,125(61.88％)of which were gram-negative bacteria.There were significant differences in the levels of serum miR-155,miR-141,IL-22 and IL-17 between the infection group and the no infection group(P＜0.05),the biomarker with the greatest difference value was miR-141(t=37.145,P＜0.001).As compared with the patients with different therapeutic outcomes in the infection group,there were significant differences in the levels of serum miR-155,miR-141,IL-22 and IL-17 between the survival group and the death group(P＜0.05),and the index with the greatest difference value was IL-17(t=35.848,P＜0.001).The values of the four markers in prediction of the therapeutic outcomes of the CRF HD patients compli-cated with hospital-associated infections were analyzed by ROC curves,and the area under the curve(AUC)of the joint detection 0.922 was the highest(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CRF HD patients complicated with hospital-associated infections.The levels of se-rum miR-155,miR-141,IL-22 and IL-17 are elevated with the incidence of infections and deterioration of progno-sis.The joint detection of the markers has high predictive value.

Objective:To observe the incidence of early blood eosinophils (Eos) elevation in patients with peritoneal dialysis (PD), analyze its related factors, and its relationship with early-onset peritonitis in PD patients.Methods:This study was a retrospective observational cohort study. Patients who underwent PD catheterization in Peking University People's Hospital from January 2012 to December 2022 were included. After surgery, PD treatment was started immediately and followed up regularly ≥12 months. The general information and laboratory indexes collected 1 week before catheterization, and at 1, 3, 6 and 12 months after catheterization were recorded. The occurrence of elevated blood Eos (≥0.5×10 9/L) during the early stage of PD, the related factors of Eos elevation (≥0.5×10 9/L) and the relationship with early-onset peritonitis (within 12 months after PD initiation) were analyzed. Results:(1) A total of 235 patients were enrolled, with an age of (57.9.±13.9) years, including 136 males (57.9%). The primary diseases were predominantly chronic glomerulonephritis (111/235, 42.7%) and diabetic nephropathy (83/235, 35.3%). During the 12-month follow-up period, 73 patients had elevated blood Eos (31.1%), of which 37 cases (50.7%) occurred within 1 month after PD catheterization, 21 cases (28.7%) occurred 2-3 months after PD catheterization, 12 cases (16.4%) occurred 4-6 months after PD catheterization, and 3 cases (4.1%) occurred 7-12 months after PD catheterization. In 73 patients with elevated Eos, 69 cases (94.5%) were mildly elevated, 4 cases (5.5%) were moderately elevated. As for the duration of elevated blood Eos, 28 cases (38.4%) lasted less than 1 month, 27 cases (37.0%) lasted 1-3 months, and 18 cases (24.7%) lasted more than 3 months. (2) In patients with elevated blood Eos, the proportion of male patients (71.4% vs. 52.1%, χ 2=7.515, P=0.006), the proportion of diabetes mellitus (55.7% vs. 41.2%, χ 2=4.168, P=0.046), and the proportion of combined vascular disease (32.9% vs. 18.2%, χ 2=6.060, P=0.017) were significantly higher than those patients in normal blood Eos group. (3) Multivariate Logistic regression analysis showed that male was an independent related factor for elevated blood Eos (≥0.5×10 9/L) in the early stages of PD ( OR=2.044, 95% CI 1.101- 3.794, P=0.023). (4) Diabetes mellitus ( OR=3.363, 95% CI 1.087-10.405, P=0.035), lower baseline hemoglobin level ( OR=0.941, 95% CI 0.903-0.980, P=0.004) and elevated blood Eos (with serum Eos<0.5×10 9/L as reference, OR=2.917, 95% CI 1.022-8.326, P=0.045) were the independent related factors of early-onset peritonitis. Conclusion:Blood Eos elevations are common in early stage of PD patients , mainly occuring within 6 months after PD catheterization, and most of them are slightly increased and last less than 3 months. Male sex is an independent related factor for the elevation of blood Eos in the early stage of PD. Elevated blood Eos is an independent related factor for early-onset peritonitis.

OBJECTIVE To observe the expressions of microribonucleic acid(miR)-155,miR-141,interleukin(IL)-22 and IL-17 in peripheral blood of the chronic renal failure(CRF)and hemodialysis(HD)patients compli-cated with hospital-associated infections and analyze the clinical treatment outcomes.METHODS A total of 561 CRF patients who underwent HD in Wuhan First Hospital from Jun.2022 to Jun.2023 were enrolled in the study and were divided into the infection group with 182 cases and the non-infection group with 379 cases according to the status of hospital-associated infections.The patients of the infection group were divided into the survival group with 138 cases and the death group with 44 cases according to the clinical therapeutic outcomes of a 6-month fol-low-up.The distribution of pathogens isolated from the CRF HD patients with hospital-associated infections was analyzed,the clinical data were compared between the infection group and the non-infection group;the levels of serum miR-155,miR-141,IL-22 and IL-17 were observed and compared among the groups.The values of the se-rologic markers in prediction of the clinical therapeutic outcomes of the CRF HD patients with hospital-associat-ed infections were analyzed by receiver operating characteristic(ROC)curves.RESULTS The proportions of pa-tients with no less than 1 year of hemodialysis,femoral venous catheter indwelling and long-term catheter indwell-ing were higher in the infection group than those in the non-infection group(P＜0.05).Totally 202 strains of pathogens were isolated from the infection group,125(61.88％)of which were gram-negative bacteria.There were significant differences in the levels of serum miR-155,miR-141,IL-22 and IL-17 between the infection group and the no infection group(P＜0.05),the biomarker with the greatest difference value was miR-141(t=37.145,P＜0.001).As compared with the patients with different therapeutic outcomes in the infection group,there were significant differences in the levels of serum miR-155,miR-141,IL-22 and IL-17 between the survival group and the death group(P＜0.05),and the index with the greatest difference value was IL-17(t=35.848,P＜0.001).The values of the four markers in prediction of the therapeutic outcomes of the CRF HD patients compli-cated with hospital-associated infections were analyzed by ROC curves,and the area under the curve(AUC)of the joint detection 0.922 was the highest(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CRF HD patients complicated with hospital-associated infections.The levels of se-rum miR-155,miR-141,IL-22 and IL-17 are elevated with the incidence of infections and deterioration of progno-sis.The joint detection of the markers has high predictive value.

Objective:To observe the incidence of early blood eosinophils (Eos) elevation in patients with peritoneal dialysis (PD), analyze its related factors, and its relationship with early-onset peritonitis in PD patients.Methods:This study was a retrospective observational cohort study. Patients who underwent PD catheterization in Peking University People's Hospital from January 2012 to December 2022 were included. After surgery, PD treatment was started immediately and followed up regularly ≥12 months. The general information and laboratory indexes collected 1 week before catheterization, and at 1, 3, 6 and 12 months after catheterization were recorded. The occurrence of elevated blood Eos (≥0.5×10 9/L) during the early stage of PD, the related factors of Eos elevation (≥0.5×10 9/L) and the relationship with early-onset peritonitis (within 12 months after PD initiation) were analyzed. Results:(1) A total of 235 patients were enrolled, with an age of (57.9.±13.9) years, including 136 males (57.9%). The primary diseases were predominantly chronic glomerulonephritis (111/235, 42.7%) and diabetic nephropathy (83/235, 35.3%). During the 12-month follow-up period, 73 patients had elevated blood Eos (31.1%), of which 37 cases (50.7%) occurred within 1 month after PD catheterization, 21 cases (28.7%) occurred 2-3 months after PD catheterization, 12 cases (16.4%) occurred 4-6 months after PD catheterization, and 3 cases (4.1%) occurred 7-12 months after PD catheterization. In 73 patients with elevated Eos, 69 cases (94.5%) were mildly elevated, 4 cases (5.5%) were moderately elevated. As for the duration of elevated blood Eos, 28 cases (38.4%) lasted less than 1 month, 27 cases (37.0%) lasted 1-3 months, and 18 cases (24.7%) lasted more than 3 months. (2) In patients with elevated blood Eos, the proportion of male patients (71.4% vs. 52.1%, χ 2=7.515, P=0.006), the proportion of diabetes mellitus (55.7% vs. 41.2%, χ 2=4.168, P=0.046), and the proportion of combined vascular disease (32.9% vs. 18.2%, χ 2=6.060, P=0.017) were significantly higher than those patients in normal blood Eos group. (3) Multivariate Logistic regression analysis showed that male was an independent related factor for elevated blood Eos (≥0.5×10 9/L) in the early stages of PD ( OR=2.044, 95% CI 1.101- 3.794, P=0.023). (4) Diabetes mellitus ( OR=3.363, 95% CI 1.087-10.405, P=0.035), lower baseline hemoglobin level ( OR=0.941, 95% CI 0.903-0.980, P=0.004) and elevated blood Eos (with serum Eos<0.5×10 9/L as reference, OR=2.917, 95% CI 1.022-8.326, P=0.045) were the independent related factors of early-onset peritonitis. Conclusion:Blood Eos elevations are common in early stage of PD patients , mainly occuring within 6 months after PD catheterization, and most of them are slightly increased and last less than 3 months. Male sex is an independent related factor for the elevation of blood Eos in the early stage of PD. Elevated blood Eos is an independent related factor for early-onset peritonitis.

Objective:Peritoneal dialysis(PD)-associated peritonitis is a common and major complica-tion of PD and the most common cause of technical failure of PD.The presence of bacterial biofilm may be an important factor leading to refractory or recurrence of peritonitis.To investigate the formation and characteristics of bacterial biofilms on PD catheters after peritonitis-associated catheter removal.Methods:The patients with maintenance PD who were regularly followed up in the Peking University People's Hospital from June 2007 to January 2022 were retrospectively analyzed.The patients who with-drew from PD because of peritonitis and removed the PD catheter in our hospital and underwent the scan-ning electron microscope examination of the catheter were selected.The general information of the pa-tients,the electron microscope results of the PD catheter and the bacterial culture results of the PD fluid were summarized.Results:(1)A total of 18 patients were included,11 were female(accounting for 61.1％).The average age of the patients was(59.1±11.5)years,and the average duration of dialysis was(80.1±47.4)months.Primary kidney diseases were predominantly chronic glomerulonephritis(55.6％),followed by diabetic nephropathy(27.8％),and others(16.6％).The reasons for cathe-ters removal in 18 patients were refractory peritonitis in 11 cases,recurrent peritonitis in 5 cases,and fungal peritonitis in 2 cases.(2)16 of the 18 patients(88.9％)had catheter bacterial biofilm,and the bacterial biofilm forms were all cocci.Some were arranged in grape-like shapes,and their diameters ranged from about 500 nm to 1 000 nm.The bacterial culture results of peritoneal dialysis fluid showed that the three most common pathogens were Escherichia coli,methicillin-sensitive Staphylococcus aureus(MSSA),and Staphylococcus epidermidis.(3)Among the 18 patients enrolled,13 patients(72.2％)had peritonitis in the past.The causative bacteria of peritonitis in 9 patients were cocci,including coagu-lase-negative Staphylococci(Staphylococcus suis,Staphylococcus surface,Staphylococcus xylosus,Staphy-lococcus warneri),Staphylococcus aureus,Streptococcus(Streptococcus salivarius and Aerococus viridans).Conclusion:Bacterial biofilm formation on the inner surface of PD catheter is common in peritonitis-asso-ciated catheter removal patients.Not all PD catheters removed due to peritonitis have bacterial biofilms.Bacterial biofilms and peritonitis pathogens may not be consistent.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.

Objective:To analyze the expression of CD27 on T lymphocytes in the microenvironment of multiple myeloma (MM), and explore whether CD27 level or the CD27-/CD27+ ratio of T-cell affect the prognosis of MM patients.Methods:A total number of 103 newly-diagnosed MM patients from January 2016 to June 2019 were enrolled in the Affiliated Cancer Hospital of Harbin Medical University. All patients received bortezomib-based three-drugs combination regimen. The expression of CD27 on T lymphocytes in bone marrow aspirate samples was detected by flow cytometry before any treatment. MM patients were divided into two groups according to the CD27 level: CD27-high expression group (CD27 expression on T-cells ≥20%) and CD27-low expression group (CD27 expression on T-cells <20%). The clinical characteristics, treatment response and prognosis of patients between the two groups were analyzed using χ 2-test. The survival and clinical information of patients were compared using Kaplan-Meier method, and the related factors related to the survival of MM were analyzed using Cox proportional risk model. Results:Among 103 MM patients, 68 cases (66.0%) were included in CD27 high expression group, and 35 cases (34.0%) were included in low expression group. The percentage of bone marrow plasma cells and β2-MG level in CD27 high expression group were higher than those in CD27 low expression group significantly (54.4% [37/68] vs 22.9% [8/35], χ2=9.352, P=0.002;58.8% [40/68] vs 37.1% [13/35], χ2=4.348, P=0.037), and the proportion of ISS stage Ⅱ-Ⅲ in CD27 high expression group was higher than the counterpart (79.4% [54/68] vs 60% [21/35], χ2=4.399, P=0.036). After 4 cycles of three-drug combination therapy, the overall response rate ( ORR=stringent complete response+complete response+very good partial response+partial response) of the low CD27 expression group was higher than the high expression group (82.9% [29/35] vs 38.2% [26/68], χ2=18.489, P<0.01). The deep response rate to treatment (stringent complete response+complete response+very good partial response) was higher (48.6% [17/35] vs 27.9% [19/68], χ2=4.326, P=0.038), and the progression, free surviva (PFS) was longer (21months vs.14.1months, t=18.655, P<0.001) in the low expression group compared with CD27-high group. Univariate analysis showed that CD27-/CD27+T lymphocyte ratio, ISS stage Ⅱ-Ⅲ, age ≥65 years, β2-Mg ≥3.5 mg/L, and plasma cell proportion ≥30% were associated with the poor prognosis of MM patients, and the differences were significant statistically ( P<0.05). Multivariate analysis showed that CD27-/CD27+T lymphocyte ratio was an independent prognostic factor for 2-year overall survival (OS)( HR=2.425, 95% CI 1.216-4.835, P=0.012) and 2-year PFS ( HR=1.881, 95% CI 1.085-3.260, P=0.024) in MM patients. Conclusions:The expression of CD27 in T lymphocytes is correlated with the prognosis, treatment response and progression-free survival of MM. The ratio of CD27-/CD27+T lymphocytes is an independent prognostic indicator.

Objective:To study the thickness of cervical squamous epithelia and its correlation with cervical precancerous lesions.Methods:We selected 495 HE slides of 209 cervical biopsies from January 2020 to June 2020 in the Department of Pathology, the First and Seventh Medical Center of the PLA General Hospital, including 173 slides with low grade squamous intraepithelial lesion (LSIL) and 214 slides with high grade squamous intraepithelial lesion (HSIL). Artificial intelligence labeling software was used to assist in measuring the epithelial thickness of normal cervical squamous epithelium, LSIL and HSIL of each slide. The thickest, thinnest, and middle widths of epithelial thickness were measured, respectively. Average epithelial thickness was defined as the sum of the above three widths divided by 3. The correlation statistical analysis was performed by combining the data of age and pathological diagnosis.Results:The average thickness of normal cervical squamous mucosa was (245.83±91.40) μm, which was (222.42±81.22) μm and was (195.95±66.59) μm in LSIL and HISL epithelial respectively ( F=27.09, P<0.01). The average cell layers of normal cervical squamous epithelium was (15.5±4.2) layers, which of LSIL was (14.8±4.8) layers, and that of HSIL was (15.8±4.8) layers. The differences among normal, LSIL and HSIL were not statistically significant ( P>0.05). Further statistical analysis was stratified by age (≤30 years, 31-40 years, 41-50 years, 51-60 years, and >60 years), the results of Pearson correlation analysis showed that the thickness of normal cervical squamous epithelial gradually thinned with age (correlation coefficient r=-0.141 9, P<0.05), while LSIL and HSIL epithelial thickness had significant correlation with age ( P>0.05). In the subgroup of ≤50 years old, the epithelial thickness of normal squamous epithelium was the thickest, followed by LSIL, and HSIL epithelial thickness was the thinnest. The differences were statistically significant ( P<0.05). While in the subgroup of >50 years, the differences were not statistically significant ( P>0.05). Conclusions:The cervical squamous epithelium gradually becomes thinner with the degree of precancerous lesions increasing among patients of ≤50 years old. However, after age of 50 years, with the onset of menopause, the normal mucosal epithelium is becoming atrophy, so that mucosal thickness is no longer correlated with the extent of the lesion. In addition, it is suggested that the cervical vinegar white test performance during colposcopy is related to the protein changes in the mucosal epithelial cells, but not directly related to the thickness of the epithelial layer.

Epstein-Barr virus (EBV) positive diffuse large B cell lymphoma (DLBCL) is a rare type of B cell lymphoma associated with chronic EBV infection. The main subtype is activated B cell-like and it′s invasive. The response to combined chemotherapy is worse than that of EBV negative patients, and the prognosis is poor. As the researches on pathogenesis and biological characteristics of EBV positive DLBCL deepen, new therapeutic strategies are emerging, such as antiviral therapy, monoclonal antibody, inhibitors of signaling pathway and immunotherapy including cellular immunotherapy and immune checkpoint inhibitor. These new therapeutic strategies can improve the efficacy and reduce the occurrence of adverse reactions.