Objective:To compare the efficacy and safety of irradiation-incorporated and chemotherapy only-based myeloablative conditioning regimens in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for patients with high-risk myeloid malignancies.Methods:This study retrospectively collected clinical data from 63 high-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients who underwent haplo-HSCT at the Fifth Medical Center of the Chinese PLA General Hospital from January 2015 to December 2019. These patients were classified into the irradiation ( n = 17) and chemotherapy ( n = 46) groups based on different conditioning regimens. The differences between the two groups were compared in terms of hematopoietic reconstitution, cumulative incidence of acute/chronic graft-versus-host diseases (aGVHD and cGVHD), non-relapse mortality (NRM), relapse rate (RR), overall survival (OS), and disease-free survival (DFS), followed by the analysis of prognostic factors. Results:The median follow-up time for the irradiation and chemotherapy groups was 78.5 and 72.3 months, respectively. The median time for neutrophil engraftment was 14.0 days in the irradiation group and 14.5 d in the chemotherapy group, and for platelet engraftment was 15.0 and 13.0 d, respectively. As a result, the two groups showed no statistically significant differences in hematopoietic reconstitution ( P > 0.05). The cumulative incidence of aGVHD and cGVHD was higher in the irradiation group compared to the chemotherapy group, yet showing no statistically significant differences ( P > 0.05). Specifically, the cumulative incidence of grade Ⅱ-Ⅳ aGVHD within 100 d was 29.4% and 21.7% for the irradiation and chemotherapy groups, respectively. The cumulative incidence of grade Ⅲ-Ⅳ aGVHD was 23.5% and 13.0%, respectively. The cumulative incidence of severe cGVHD within five years was 11.8% in the irradiation group and 8.7% in the chemotherapy group. In terms of long-term survival, the cumulative 5\|year RR and NRM were 20.2% and 28.4% in the irradiation group, 5.9% and 23.9% in the chemotherapy group, respectively, showing no statistically significant differences ( P > 0.05). The 5-year DFS and OS rates were 73.9% and 47.7% in the irradiation group, and 81.1% and 54.4% in the chemotherapy group, respectively, without statistically significant differences ( P > 0.05). Notably, the irradiation group manifested more favorable DFS and OS survival curves compared to the chemotherapy group. The survival curves indicate that the irradiation-incorporated regimen exhibited better trends in OS, DFS, and cGVHD-free relapse-free survival (GRFS). However, multivariate analysis did not reveal that irradiation conditioning is an independent prognostic factor affecting survival [ HR = 0.532 (0.163-1.735), 0.370 (0.091-1.516), 0.683 (0.248-1.882), P > 0.05]. Conclusions:In haplo-HSCT for high-risk myeloid malignancies, the irradiation-incorporated conditioning regimen demonstrates lower RR and NRM, higher DFS and OS, and potentially superior survival outcomes compared to the chemotherapy only-based regimen. Therefore, the irradiation-incorporated conditioning regimen may be preferentially considered in haplo-HSCT.

Objective:To compare the efficacy and safety of irradiation-incorporated and chemotherapy only-based myeloablative conditioning regimens in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for patients with high-risk myeloid malignancies.Methods:This study retrospectively collected clinical data from 63 high-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients who underwent haplo-HSCT at the Fifth Medical Center of the Chinese PLA General Hospital from January 2015 to December 2019. These patients were classified into the irradiation ( n = 17) and chemotherapy ( n = 46) groups based on different conditioning regimens. The differences between the two groups were compared in terms of hematopoietic reconstitution, cumulative incidence of acute/chronic graft-versus-host diseases (aGVHD and cGVHD), non-relapse mortality (NRM), relapse rate (RR), overall survival (OS), and disease-free survival (DFS), followed by the analysis of prognostic factors. Results:The median follow-up time for the irradiation and chemotherapy groups was 78.5 and 72.3 months, respectively. The median time for neutrophil engraftment was 14.0 days in the irradiation group and 14.5 d in the chemotherapy group, and for platelet engraftment was 15.0 and 13.0 d, respectively. As a result, the two groups showed no statistically significant differences in hematopoietic reconstitution ( P > 0.05). The cumulative incidence of aGVHD and cGVHD was higher in the irradiation group compared to the chemotherapy group, yet showing no statistically significant differences ( P > 0.05). Specifically, the cumulative incidence of grade Ⅱ-Ⅳ aGVHD within 100 d was 29.4% and 21.7% for the irradiation and chemotherapy groups, respectively. The cumulative incidence of grade Ⅲ-Ⅳ aGVHD was 23.5% and 13.0%, respectively. The cumulative incidence of severe cGVHD within five years was 11.8% in the irradiation group and 8.7% in the chemotherapy group. In terms of long-term survival, the cumulative 5\|year RR and NRM were 20.2% and 28.4% in the irradiation group, 5.9% and 23.9% in the chemotherapy group, respectively, showing no statistically significant differences ( P > 0.05). The 5-year DFS and OS rates were 73.9% and 47.7% in the irradiation group, and 81.1% and 54.4% in the chemotherapy group, respectively, without statistically significant differences ( P > 0.05). Notably, the irradiation group manifested more favorable DFS and OS survival curves compared to the chemotherapy group. The survival curves indicate that the irradiation-incorporated regimen exhibited better trends in OS, DFS, and cGVHD-free relapse-free survival (GRFS). However, multivariate analysis did not reveal that irradiation conditioning is an independent prognostic factor affecting survival [ HR = 0.532 (0.163-1.735), 0.370 (0.091-1.516), 0.683 (0.248-1.882), P > 0.05]. Conclusions:In haplo-HSCT for high-risk myeloid malignancies, the irradiation-incorporated conditioning regimen demonstrates lower RR and NRM, higher DFS and OS, and potentially superior survival outcomes compared to the chemotherapy only-based regimen. Therefore, the irradiation-incorporated conditioning regimen may be preferentially considered in haplo-HSCT.

Objective To systematically assess the spatiotemporal distribution,risk factors,and future trends of chronic obstructive pulmonary disease(COPD)among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease(GBD)data in order to provide support for the formulation of prevention and control strategies of the disease.Methods The GBD data from 1990 to 2021 were analyzed for the incidence,mortality,disability-adjusted life years(DALYs),and estimated annual percentage change(EAPC)of COPD in<50-year-old individuals across 204 countries and regions.The data were stratified by age,sex,region,country,and sociodemographic index(SDI).The COPD trends until 2035 were predicted.Results In 2021,the global incidence of early-onset COPD was estimated at 2.5 million cases(95%uncertainty interval:2.09～2.96 million),representing a 50.55%increase compared to 1990.Significant regional heterogeneity was observed,with low SDI regions experiencing a 134.08%increase,whereas high SDI regions exhibited a rise-then-fall trend.Risk factor analysis identified environmental and occupational exposures(air pollution,ambient ozone pollution,household air pollution from solid fuels,etc.)and smoking as the primary etiological factors.Notably,household solid fuel exposure accounted for 50.90%of COPD-related deaths in low SDI regions,compared to only 0.03%in high SDI regions.Projections indicated that by 2035,the global burden of early-onset COPD will increase to 2.59 million cases.Conclusion The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021,with pronounced disparities across regions and socioeconomic levels.COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution,and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.

Objective To investigate the clinical effect and hearing loss of endolymphatic sac decompression(ESD)combined with one or two semicircular canal obstruction(SCO)in treating the patient with stage Ⅲ or stageⅣ Meniere disease.Methods Forty-three patients with stage Ⅲ or stage Ⅳ Meniere disease,who failed to respond to conventional conservative treatment and had the expectation of preserving residual hearing function,were enrolled in the study.They were divided into three groups according to the operation they underwent:ESD combined with lateral and posterior semicircular canal obstruction(ESD+LPSCO)13 cases,ESD combined with lateral semicircu-lar canal obstruction(ESD+LPSCO)14 cases,and ESD only 16 cases.Data of vertigo,ear fullness and tinnitus be-fore and after operation was collected,analyzed and compared.Hearing function before and after the operation was also evaluated.Results The number of vertigo attacks in the three groups(ESD+LPSCO,ESD+LSCO,and ESD)were all significantly reduced after operation.The vertigo control rate were 92.3％,78.6％and 62.5％re-spectively.Compared with pre-operation,the vertigo severity post-operation in the three groups were also signifi-cantly reduced.And the improvement rate of vertigo severity after ESD+LPSCO and ESD+LSCO were both 100％,which were significantly higher than that of ESD(68.8％).The discomfort of tinnitus and ear fullness in the three groups were significantly improved compared with that of pre-operation.The improvement rates of tinnitus in the three groups were 46.2％,50.0％and 43.8％respectively,with no significant difference.The improvement rate of ear fullness in the three groups were 61.5％,57.1％and 50.0％respectively,with no significant difference either.The proportion of patients with decreased hearing after operation in the three groups was 15.4％,7.1％and 18.8％,respectively,and the differences were insignificant.Conclusion ESD combined with one or two SCO can effectively control vertigo and other symptoms of patients with stage Ⅲ or Ⅳ Meniere's disease who had failure to conventional conservative treatment,and can preserve the residual hearing function in considerable extent.

Objective To investigate the effects of long-term occupational exposure to high-frequency noise in specific frequency bands on auditory function of the inner ear,and to evaluate the mechanisms of auditory threshold damages due to high-frequency noise exposure utilizing bone conduction audiometry and acoustic physical models.Methods The study subjects included factory workers and airport ground staff working in high-noise environments for a long period.Two groups(an exposure group and a control group)were established,and the exposure group was further divided into 3 subgroups according to exposure duration:5-9 years,10-14 years,and over 15 years.Bone conduction audiometry was used to assess auditory threshold changes in different frequency bands(4,6,8 kHz),while a sound level meter was employed to record noise exposure intensity.The impact of noise on the cochlea was simulated using an acoustic physical model.Multivariable regression analysis,controlling for confounding factors such as age and gender,was used to further analyze the independent effects of exposure duration and intensity on auditory damage.Results The auditory thresholds of exposure group were significantly higher than those of control group in the high-frequency bands,particularly in 8 kHz frequency band(P＜0.001).With increasing exposure duration,auditory damage in exposure group progressively worsened,and the most significant auditory threshold changes was found in the group exposed for over 15 years.The predictions made by the acoustic physical model closely matched the actual measurements,and the high model fitting degree(R2:0.85-0.90)in the long-term exposure group indicated a strong predictive capability for the cumulative effects of cochlear damage.Conclusion Long-term exposure to high-frequency noise in specific frequency bands results in significant cumulative damage to auditory function of the inner ear.Exposure duration and intensity are the primary independent risk factors.

Objective To assess the methodology,reporting quality and intervention reporting quality of randomised controlled trials(RCT)of acupuncture for chronic obstructive pulmonary disease(COPD).Methods Randomized controlled trials of acupuncture for the treatment of chronic obstructive pulmonary disease from the establishment of the database to March 1,2023 through computer system search of CNKI,Wanfang,VIP,SinoMed,and PubMed databases.Two researchers independently conducted literature search,relevant data extraction,etc.,and assessed the quality of reports using the bias assessment tools ROB2,CONSORT Extended Statement and STRICTA List of Cochrane Systematic Review Manuals.Results After excluding non-compliant articles through the developed exclusion criteria,31 RCT remained.A methodological assessment of the included RCT according to the Cochrane website bias assessment tool ROB2 showed that 9 studies(29.03%)were at high risk of bias and no studies at low risk of bias.The CONSORT extended statement based on non-drug randomized controlled trials evaluated the quality of the literature,indicating that the reporting rate in terms of methods,results,trial protocol registration,etc.was low.The results of the evaluation according to the entries in the STRICTA list show that most of the literature does not describe the details of acupuncture and the background of the therapist in sufficient detail,but the reasonableness of acupuncture treatment is relatively complete.Conclusion At present,the quality of randomized controlled trials of acupuncture for COPD is generally low,and it is recommended that future researchers strictly follow the internationally recognized CONSORT statement and STRICTA list for trial protocol design and study result reporting.

Objective : The CRISPR / dCas9-SAM system was used to explore genes related to the proliferation of gastric cancer cells AGS，and their role in the occurrence and development of gastric cancer was analyzed． Methods : sgRNA was designed for genes with differential expression between gastric cancer and normal gastric tissue， and a lentiviral library was obtained after packaging was constructed．The AGS cells at different time points after the library was infected with AGS cells were used as the screening pressure，and the AGS cells at three time points on days 0，7 and 14 were collected．High-throughput sequencing analyzed sgRNA enrichment in AGS cells at dif- ferent time points after infection to obtain differential genes related to AGS cell proliferation. Results : Bioinformat- ics showed that compared with the 0 d group，42 and 45 negative screening differential genes and 59 and 40 posi- tive screening differential genes were obtained in the 7 d group and 14 d group，respectively．Among them，the 7 d group and the 14 d group had 11 genes in the negative screening and the positive screening． Conclusion In this study，11 genes inhibiting the proliferation of AGS cells were screened，of which 5 were protein-coding genes and 6 were long non-coding RNA ( lncRNA ) genes． 11 candidate genes that promoted AGS cell proliferation were screened，of which 3 were protein-coding genes and 8 were lncRNA genes．It laid a foundation for further function- al verification and comprehensive analysis of the occurrence and development process of gastric cancer.

Objective::Calcific aortic valve disease (CAVD) affects millions of elderly people, and there is currently no effective way to stop or slow down its progression. Therefore, exploring the pathogenesis of CAVD is very important for prevention and treatment. Cartilage oligomeric matrix protein (COMP) have important role in cell phenotype change. This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.Methods::Human aortic valve tissues from Nanjing First Hospital (CAVD group, n=20; control group, n=11) were harvested. The expression level of COMP was tested by western blot and immunohistochemistry. Dual immunofluorescence staining was used for locating COMP. Bone morphogenetic protein-2 (BMP2) signalling were tested by western blot. The animal model was also used to detect COMP level by immunohistochemistry. Results::The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve ( P<0.05); COMP was expressed near the calcific nodules and co-localized with α-smooth muscle actin (α-SMA). The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group ( P<0.05). Furthermore, immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves. Conclusions::The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.

Objective::Calcific aortic valve disease (CAVD) affects millions of elderly people, and there is currently no effective way to stop or slow down its progression. Therefore, exploring the pathogenesis of CAVD is very important for prevention and treatment. Cartilage oligomeric matrix protein (COMP) have important role in cell phenotype change. This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.Methods::Human aortic valve tissues from Nanjing First Hospital (CAVD group, n=20; control group, n=11) were harvested. The expression level of COMP was tested by western blot and immunohistochemistry. Dual immunofluorescence staining was used for locating COMP. Bone morphogenetic protein-2 (BMP2) signalling were tested by western blot. The animal model was also used to detect COMP level by immunohistochemistry. Results::The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve ( P<0.05); COMP was expressed near the calcific nodules and co-localized with α-smooth muscle actin (α-SMA). The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group ( P<0.05). Furthermore, immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves. Conclusions::The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.

Objective: This study was designed to evaluate the clinical value of seven combinedtumor-associated autoantibodies (7-TAAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods: This is a cross-sectional study. The 81 newly diagnosed patients with NSCLC were enrolled. 46 patients with benign pulmonary diseases (BLD) and 55 healthy subjects were selected as the BLD group and the healthy control (HC) group, respectively. ELISA was used to detect the concentration of seven TAABs of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE in the serum of the NSCLC and the other two groups. The levels of lung cancer tumor markers CEA, NSE, SCC and CYFRA21-1 in serum were also detected in all enrolled subjects. Kruskal-wallis test was used for comparison among the three groups, Mann-Whitney test was used to evaluate the differences between the two groups, and positivity rates were analyzed by using standard χ² tests and Fisher exact tests. The receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic efficacy of 7-TAAB or combination of 7-TAAB and traditional tumor markers. Results: The serological levels of six TAABs (p53, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in the NSCLC group were higher than that in the BLD group (p53: Z=-4.370, P=0.000; SOX2: Z=-4.412, P=0.000; GAGE7: Z=-4.250, P=0.001; GBU4-5: Z=-2.678, P=0.025; MAGE A1: Z=-4.504, P=0.002; CAGE: Z=-4.646, P=0.001) and the HC group (p53: Z=-3.543, P=0.000; SOX2: Z=-3.383, P=0.002; GAGE7: Z=-4.893, P=0.001; GBU4-5: Z=-3.381, P=0.025; MAGE A1: Z=-3.369, P=0.001; CAGE: Z=-2.981, P=0.002),respectively. The differences were statistically significant. The comparison of PGP9.5 in NSCLC group with that in the BLD group was statistically significant (Z=-2.871, P=0.044), with that in the HC group was no difference (Z=-2.280, P=0.05). None of the seven TAABs showed a significant difference between the BLD group and the HC group (p53: Z=-1.917, P=0.917; PGP9.5: Z=-1.228, P=0.966; SOX2: Z=-1.789, P=0.325; GAGE7: Z=-0.563, P=1.000; GBU4-5: Z=-0.315, P=0.985; MAGE A1: Z=-2.310, P=0.857; CAGE: Z=-2.822, P=0.703). According to the criteria of cut-off value, the detection value of individual TAAB was judged as negative or positive. The specificity of every single TAAB to NSCLC was ≥89%, but the sensitivity was ≤39.5%. Positive in any of the single TAAB was considered as a positive result of 7-TAAB, the positive rate of 7-TAAB in NSCLC subgroups with early stages (stageⅠand stageⅡ) was considered higher than that of traditional biomarkers (7-TAAB:52.94%, CEA: 23.53%, NSE: 8.82%, CYFRA21-1∶20.59%, SCC:14.71%), and 7-TAAB was more sensitive to NSCLC patients with poor prognosis, such as advanced stages (stageⅢand stageⅣ) and moderately-poorly differentiation. The AUC of 7-TAAB was 0.734, with a sensitivity of 66.67% and a specificity of 80.20%. In coordination with 7-TAAB, CEA, NSE, CYFRA21-1 and SCC, the AUC was 0.917, with a sensitivity of 87.70% and a specificity of 81.20%. Conclusions 7-TAAB, regarded as a panel of serological markers, is helpful in NSCLC diagnosis and shows broad application prospect. The detection rate of 7-TAAB in patients with early NSCLC is superior to that of traditional serum tumor markers, and the combination of 7-TAAB with CEA, NSE CYFRA21-1 and SCC could improve the diagnosis sensitivity of patients with NSCLC.