BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Objective:To evaluate the effect of automated flexible endoscope channel brushing system (AFECBS) on endoscope reprocessing.Methods:A prospective randomized controlled study was conducted. The used endoscopes were divided into automatic group and manual group by random number table method, 200 in each group. In the automatic group, the AFECBS was used to scrub each tube 3 times during endoscope cleaning; and in the manual group, scrubbing and disinfection personnel routinely brushed each pipeline for 3 times. The primary end point was the qualified rate of endoscopic cleaning quality in the two groups, and the secondary end point was the time spent by the scrubbing and disinfection personnel on the two groups.Results:The qualified rate of overall cleaning in the automatic group was 90.0% (180/200), and in the manual group was 81.0% (162/200). The qualified rate of the automatic group was higher than that of the manual group ( χ2=6.534, P=0.011). The qualified rate of gastroscope cleaning in the automatic group was higher than that in the manual group [92.0% (127/138) VS 81.6% (120/147), χ2=6.658, P=0.010]. There was no significant difference in the qualified rate of colonoscope cleaning between the automatic group and the manual group [85.5% (53/62) VS 79.2% (42/53), χ2=0.774, P=0.379]. When the cleaning personnel scoured 5 endoscopes in each of the two groups, the time of the automatic group (5.17±0.42 min) was shorter than that of the manual group (9.60±0.53 min) ( t=92.644, P<0.001). Conclusion:Compared with manual scrubbing, AFECBS can improve the qualified rate of endoscope cleaning and the work efficiency of scrubbing and disinfection personnel, which is worthy of clinical application.

Objective:To investigate the relationship between spread through air spaces(STAS) of peripheral stage ⅠA small adenocarcinoma of the lung(≤2 cm) and related factors such as clinical and CT morphological features, and to construct a nomogram model.Methods:Relevant clinical, pathological and imaging data of patients who underwent lung surgery and were diagnosed as peripheral stage ⅠA small lung adenocarcinoma by postoperative pathology in the Affiliated Hospital of Nantong University from 2017 to 2022 were collected, of which cases that met the inclusion criteria from 2017 to 2021 served as the training group, and those that met the inclusion criteria in 2022 served as the validation group. The independent risk factors for the occurrence of STAS in peripheral stage ⅠA lung small adenocarcinoma were investigated by using univariate analysis and multifactorial logistic regression analysis, based on which a nomogram prediction model was constructed, and the subjects were analyzed by using the receiver operating characteristic curve( ROC), correction model, etc. were used to evaluate the model. Results:A total of 430 patients who met the criteria were included, including 351 patients in the training group(109 STAS-positive and 242 STAS-negative) and 79 patients in the validation group(23 STAS-positive and 56 STAS-negative). Univariate analysis showed that the patients in the two groups showed a significant difference in age(>58 years old), gender, smoking history, tumor location(subpleural, non-subpleural), pleural pull, nodule type, nodule maximal diameter, solid component maximal diameter, consolidation tumor ratio(CTR), lobulation sign, burr sign, bronchial truncation sign, vascular sign(includes thickening and distortion of blood vessels in/around the nodes), satellite lesions, and ground-glass band sign were statistically significant( P<0.05). The results of multifactorial logistic regression analysis showed that CTR( OR=4.98, P<0.001), lobulation sign( OR=4.07, P=0.013), burr sign( OR=3.66, P<0.001), and satellite lesions( OR=3.56, P=0.009) were the independent risk factors for the occurrence of STAS. Applying the above factors to construct the nomogram model and validate the model, the results showed that the ROC curve was plotted by the nomogram prediction model, and the area under the ROC curve( AUC) of the training set was 0.840(sensitivity 0.835, specificity 0.734), and the validation set had an AUC value of 0.852(sensitivity 0.786, specificity 0.783), and the training set and validation set calibration curves have good overlap with the ideal curve. Conclusion:CTR, lobular sign, burr sign, and satellite lesions are independent risk factors for STAS, and the nomogram model constructed in this study has good predictive value.

Objective To design an effective universal DNA vaccine for influenza A virus and detect its immune efficacy in mice.Methods The DNA sequence containing the M2(3M2e)extracellular domain of H1N1,H3N2 and H9N2 subtypes of influenza A virus was synthesized and cloned into vector pVAX1 to construct eukaryotic expression plasmid pVAX1-3M2e. The plasmid pVAX1-3M2e was mixed with cell penetrating peptides(CPPs)RVG9dR,Protamine,and RVG9dR +Protamine peptide complex(1∶1)at different mass fractions(1∶0. 5,1∶1,1∶2,1∶4,and 1∶8),separately,and gel retardation was performed to determine the proper binding of DNA and CPPs. The delivery efficiency of the CPPs was detected by cell fluorescence assay at cellular level(293T cells). Male BALB/c mice were immunized intramuscularly with plasmid pVAX1-3M2e delivered by RVG9dR + Protamine(two doses:25 μg pVAX1-3M2e + 500 μg polypeptide complex,50 μg pVAX1-3M2e + 1 000 μg polypeptide complex,8 mice in each group)to detect the cross-protection effect of universal influenza A virus DNA vaccine against three subtypes of influenza viruses(H1N1,H3N2 and H9N2).Results The optimum binding ratios of DNA to RVG9dR,Protamine,and RVG9dR + Protamine were 1∶2,1∶2,and 1∶1,respectively. RVG9dR + Protamine had superior delivery efficiency to plasmid pVAX1-3M2e at the mass fraction of 1∶20. The protective rates of 50 μg pVAX1-3M2e + 1 000 μg polypeptide complex against three subtypes of influenza virus in mice were all 100%.Conclusion The plasmid pVAX1-3M2e delivered by RVG9dR + Protamine polypeptide complex provides cross protection against three subtypes of influenza A virus in mice.

Objective:To investigate the genomic profiles and immune microenvironment of olfactory neuroblastoma (ONB).Methods:Nineteen ONB cases diagnosed in the Beijing Tongren Hospital from May 2018 to October 2022 were divided into low-grade and high-grade groups according to the Hyams grading system, including 7 low-grade and 12 high-grade ONB. Whole exome sequencing and multiplex immunofluorescence analyses were performed on tissue samples of these ONB.Results:A total of 929 nonsynonymous alterations were identified in 18 of the 19 ONB (18/19) cases. The most commonly altered cancer-related genes were CTNNB1 (3/19) and ZNRF3 (3/19). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45/Mb, ranging from 0 to 3.25. The median tumor neoantigen load (TNB) was 9.39 neoantigens/Mb, ranging from 0 to 38.30. The median allelic mutation tumor heterogeneity (MATH) score was 16.95, ranging from 3.05 to 117.47. Only one of the 19 cases expressed PD-L1 (composite positive score, CPS>1) in the tumor cells. The median percentage of CD8 + tumor-infiltrating lymphocyte (TIL) in the tumor region was 1.08%. No significant differences were observed between the low-and high-grade groups for mutant genes, mutant pathways, TMB, TNB, MATH, PD-L1 expression levels, or CD8 + TILs percentage( P>0.05). However, the low-grade group showed significantly more CD68 + macrophages in both the tumor and total region than the high-grade group. Notably, CD68 +CD163 - macrophages accounted for an average of 80.52% of CD68 + macrophages. Conclusions:CTNNB1 and ZNRF3 are the most commonly altered cancer-related genes. The low expression of PD-L1 and the low percentage of CD8 + TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.

Idiopathic inflammatory myopathy(IIM)is a heterogeneous autoimmune disease of unknown etiology characterized by proximal limb muscle involvement and chronic inflammation.Multiple systems may be involved,with interstitial lung disease(ILD)being the most common manifestation of respiratory system involvement in IIM.This article summarizes the current methods of myositis animal models and myositis-associated ILD model construction methods,so as to provide reference for the subsequent construction and research of IIM-ILD models.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

ObjectiveTo compare the regulatory effects of five plant polysaccharides on immune function of cyclophosphamide （CTX）-induced immunosuppressed mice by network Meta-analysis， to provide evidence for the clinical application of polysaccharides and the development of effective polysaccharides and oligosaccharides. MethodSeven databases including PubMed， Embase and Web of Science were searched， and studies that met the inclusion criteria were selected. The methodological quality of the included studies was evaluated using the risk of bias tool of Systematic Review Centre for Laboratory Animal Experimentation （SYRCLE）， and the data were analyzed using RStudio and StataSE 17. ResultA total of 62 randomized controlled trials （RCTs） were included， involving 1 512 mice and five plant polysaccharides： Astragalus polysaccharide （APS）， lentinan （LNT）， Ganoderma lucidum polysaccharide （GLP）， Poria cocos polysaccharide （PCC）， and Codonopsis pilosula polysaccharide （CPP）. The network Meta-analysis showed that APS ranked first in increasing spleen index （mean deviation （MD）=3.54， 95% confidence interval （CI） ［2.10， 5.96］）， thymus index （MD=1.98， 95%CI ［1.55， 2.54］） and T helper cells （CD4⁺）/T suppressor cells （CD8⁺） （MD=1.63， 95%CI ［1.13， 2.37］）， while CPP ranked first in up-regulating the number of peripheral blood leukocytes （MD=24.16， 95%CI ［8.21， 71.12］）， macrophage phagocytosis index （MD=2.52， 95%CI ［1.32， 4.82］） and immunoglobulin M （IgM） content （MD=1.79， 95%CI ［1.12， 2.85］）. ConclusionAll the five plant polysaccharides can regulate the immune function of immunosuppressed mice. Among them， APS has advantages in elevating spleen index， thymus index and CD4⁺/CD8⁺， while CPP focuses on increasing the number of peripheral blood leukocytes， macrophage phagocytosis index and IgM content. Due to limited number and quality of included studies， the conclusions needs to be further verified with large samples and high-quality studies.

Objective:To investigate the feasibility and therapeutic effect of total knee arthroplasty (TKA) with cruciate-retaining (CR) prosthesis by using FEM-X1 femoral extramedullary positioning instrument based on the theory of restricted kinematic alignment (rKA).Methods:Thirty five cases who underwent total knee arthroplasty in Nanjing Drum Tower Hospital from November 2019 to December 2020 were retrospectively analyzed, including 7 males and 28 females with an average age of 71± 8 years (ranging from 55 to 85 years) Following the guidance of rKA alignment, the FEM-X1 femoral extramedullary positioning instrument was used for TKA with CR prosthesis. Before the operation, the full-length lower limb radiographs of both anteroposterior and lateral views were taken in a standing position for preoperative assessment of lateral distal femoral angle (LDFA), the medial proximal tibial angle (MPTA) and hip-knee-ankle angle (HKA). According to the principle of rKA alignment, the target LDFA, MPTA and HKA were calculated. The proximal end of tibia and distal end of femur were cut using extramedullary positioning instrument respectively. The posterior femoral condyle was cut according to the tibial plateau and mediolateral soft tissue tension. The prosthesis was installed after osteotomy. The release of collateral ligaments, PCL function, release of PCL, patellofemoral trajectory, release of patellofemoral support band, the amount of blood loss and time of operation were recorded. Postoperative LDFA, MPTA, HKA, and posterior slope angle of tibial prosthesis were measured on X-ray images. The Knee Society Score (KSS) was used for functional evaluation.Results:Thirty five cases of TKA with CR prosthesis following rKA alignment were successfully completed. The operation time was 100 (90, 110) min, and the blood loss was 100 (100, 200) ml. 30 of them were followed up for 12.5±0.7 months (ranging from 12 to 14 months). The pre-operative and post-operative LDFA were 1.0°(-2.0°, 4.0°), 0°(-2.0°, 2.0°), MPTA were -4.0°(-5.0°, -1.0°), -2.0°(-3.0°, -1.0°), HKA were -3.0°(-3.0°, -1.0°), -2.0°(-3.0°, -1.0°). There was no significant difference between the three angles before and after operation ( Z=-0.89, P=0.372; Z=1.87, P=0.061; Z=1.03, P=0.302). The average posterior tibial slope was 5°(3°, 7°). At the follow-up of one year, the KSS clinical score was 94(92, 97) and functional score was 80(70, 90) in 30 cases. During the operation, PCL was released in 1 case because of excessive tension; and lateral retinacular release was performed in 1 case because of poor patellofemoral track. Conclusion:ITKA with CR prosthesis by using the extramedullary positioning instrument on the theory of rKA alignment showed a good clinical outcome at a short follow up.

Objective:To analyze the cost-effectiveness of a relatively mature artificial intelligence (AI)-assisted diagnosis and treatment system (ENDOANGEL) for gastrointestinal endoscopy in China, and to provide objective and effective data support for hospital acquisition decision.Methods:The number of gastrointestinal endoscopy procedures at the Endoscopy Center of Renmin Hospital of Wuhan University from January 2017 to December 2019 were collected to predict the procedures of gastrointestinal endoscopy during the service life (10 years) of ENDOANGEL. The net present value, payback period and average rate of return were used to analyze the cost-effectiveness of ENDOANGEL.Results:The net present value of an ENDOANGEL in the expected service life (10 years) was 6 724 100 yuan, the payback period was 1.10 years, and the average rate of return reached 147.84%.Conclusion:ENDOANGEL shows significant economic benefits, and it is reasonable for hospitals to acquire mature AI-assisted diagnosis and treatment system for gastrointestinal endoscopy.