Objective:To evaluate the efficacy and safety of treating allogeneic hematopoietic stem cell transplantation (allo-HSCT) with azacitidine plus BUCY2 as a conditioning regimen for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).Method:From January 1, 2022 to July 15, 2023, a retrospective study was conducted for the relevant clinical data of 26 AML-MDS patients undergoing allo-HSCT with azacitidine plus BUCY2 as a conditioning regimen at Wuhan Union Hospital. There were 15 males and 11 females. For haploidentical transplantation, rabbit anti-human thymocyte immunoglobulin (ATG) was added. And tacrolimus + mycophenolale mofetil + recombinant humanized anti-CD25 monoclonal antibody injection (Xenopax) ± methotrexate were utilized for preventing GVHD. For human leukocyte antigen matched transplantation, cyclosporin A + methotrexate + Xenopax were employed for preventing GVHD. Incidence timing, severity, incidence rate of acute/chronic graft versus host disease (a/cGVHD), granulocyte/platelet engraftment time, infection type, overall survival and relapse date were recorded.Result:Granulocyte engraftment was attained with a median engraftment time of 12 (9~18) day and platelet engraftment with a median engraftment time of 16 (13~34) day. The incidence of acute graft-versus-host disease (aGVHD) was 63.14% (95% CI: 60.90%~65.37%), the incidence of grade Ⅲ aGVHD 6 (95% CI: 11.39%~13.23%) and the median onset time of aGVHD 49 (11~93) day post-transplantation. The incidence of chronic graft-versus-host disease (cGVHD) was 52.68% (95% CI: 49.23%~56.13%) and the incidence of moderate-severe cGVHD 11.43% (95% CI: 10.20%~12.66%). Infections were caused by cytomegalovirus (CMV) viremia (7 cases), bacteria (3 cases) and fungus (4 cases). Until the last follow-up, 23 recipients achieved relapse-free survival and continued MRD negativity. Death occurred due to recurrence (2 cases) and GVHD plus severe infection (1 case). Cumulative incidence of relapse (CIR) was 10.20% (95% CI: 9.21%~11.18%), 1-year overall survival (OS) 83.50% (95% CI: 67.90%~100%), GVHD/relapse-free survival (GRFS) 70.30% (95% CI: 52.30%~94.30%) and non-relapse mortality (NRM) 5.02% (95% CI: 4.53%-5.52%). Conclusion:Using azacitidine plus BUCY2 as a conditioning regimen, OS of allo-HSCT for AML-MDS is higher than that of traditional regimen. The risks of III-IV aGVHD, relapse and infection are safe and controllable.

Objective:To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients.Methods:We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison.Results:The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM ( P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM ( P=0.035) . Conclusion:This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

Objective:This study aimed to analyze the homology between carbapenem-resistant organisms (CRO) intestinal colonization strains and bloodstream infection (BSI) strains in patients undergoing hematopoietic stem cell transplantation (HSCT), confirming the clinical use of the real-time rectal swab Xpert Carba-R assay, and investigate its feasibility in early warning of BSI.Methods:Drug-resistant strains obtained from rectal swabs and blood culture samples of patients undergoing the same HSCT from January 2021 to December 2021 were collected and analyzed. The homology of the CRO intestinal colonization and BSI strains was confirmed using strain identification, antimicrobial resistance phenotyping, whole genome sequencing (WGS), multilocus sequence typing (MLST), and carbapenemase type identification. Rectal swab cultures and the real-time rectal swab Xpert Carba-R assay were conducted concurrently on patients with HSCT from August 2021 to August 2022. The accuracy of the real-time rectal swab Xpert Carba-R assay was confirmed with the sequencing results of polymerase chain reaction amplification products of the carbapenemase gene from purified colonies as a reference standard.Results:This study included 24 CRO strains from 10 patients undergoing HSCT, including 14 intestinal colonizers and 10 CRO-BSI strains. The results revealed that the CRO intestinal colonization strains and CRO-BSI strains from the same patient and their carbapenemase genes were almost identical. Additionally, WGS revealed that CRO intestinal colonization and CRO-BSI strains from the same patient were more closely related than strains from different patients. Additionally, this study included 488 rectal swab specimens from 184 patients undergoing HSCT, with CRO detection rates of 16.4% for rectal swab culture and 18.4% for the real-time rectal swab Xpert Carba-R assay. The overall sensitivity, specificity, and positive and negative predictive values of the real-time rectal swab Xpert Carba-R assay were 96.6%, 72.8%, 90.6%, and 88.9%, respectively.Conclusions:A high degree of homology was found between the CRO intestinal colonization strains and the CRO-BSI strains in patients undergoing HSCT. The real-time rectal swab Xpert Carba-R assay is a reliable and convenient method for detecting common carbapenemase genes, serving as an alternative to rectal swab culture for early warning of CRO-BSI.

Objective:This study aimed to analyze the homology between carbapenem-resistant organisms (CRO) intestinal colonization strains and bloodstream infection (BSI) strains in patients undergoing hematopoietic stem cell transplantation (HSCT), confirming the clinical use of the real-time rectal swab Xpert Carba-R assay, and investigate its feasibility in early warning of BSI.Methods:Drug-resistant strains obtained from rectal swabs and blood culture samples of patients undergoing the same HSCT from January 2021 to December 2021 were collected and analyzed. The homology of the CRO intestinal colonization and BSI strains was confirmed using strain identification, antimicrobial resistance phenotyping, whole genome sequencing (WGS), multilocus sequence typing (MLST), and carbapenemase type identification. Rectal swab cultures and the real-time rectal swab Xpert Carba-R assay were conducted concurrently on patients with HSCT from August 2021 to August 2022. The accuracy of the real-time rectal swab Xpert Carba-R assay was confirmed with the sequencing results of polymerase chain reaction amplification products of the carbapenemase gene from purified colonies as a reference standard.Results:This study included 24 CRO strains from 10 patients undergoing HSCT, including 14 intestinal colonizers and 10 CRO-BSI strains. The results revealed that the CRO intestinal colonization strains and CRO-BSI strains from the same patient and their carbapenemase genes were almost identical. Additionally, WGS revealed that CRO intestinal colonization and CRO-BSI strains from the same patient were more closely related than strains from different patients. Additionally, this study included 488 rectal swab specimens from 184 patients undergoing HSCT, with CRO detection rates of 16.4% for rectal swab culture and 18.4% for the real-time rectal swab Xpert Carba-R assay. The overall sensitivity, specificity, and positive and negative predictive values of the real-time rectal swab Xpert Carba-R assay were 96.6%, 72.8%, 90.6%, and 88.9%, respectively.Conclusions:A high degree of homology was found between the CRO intestinal colonization strains and the CRO-BSI strains in patients undergoing HSCT. The real-time rectal swab Xpert Carba-R assay is a reliable and convenient method for detecting common carbapenemase genes, serving as an alternative to rectal swab culture for early warning of CRO-BSI.

Multiple myeloma (MM) is an incurable plasma cell malignancy with a typical course characterized by response to initial treatment and eventual resistance. Despite major advances in the clinical treatment of multiple myeloma driven by the introduction of new drugs (e.g., proteasome inhibitors and immunomodulators), MM remains incurable. Nevertheless, subsequent cycles of remission and relapse continue as long as new treatments are available to patients. With the development of many new treatments, the approval of 12 new drugs over the past 15 years, and the promising trend of clinical trials, the treatment landscape has dramatically changed and patient survival has improved. This article reviews the progress of new treatments for MM.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.

Objective:To explore the influencing factors of clinically significant prostate cancer (CsPCa) in patients with PI-RADS score 3.Methods:The data of 133 consecutive patients with the PI-RADS score 3 from January 2019 to December 2020 were retrospectively analyzed. All patients underwent 4-needle transperineal targeted biopsy and 12-needle systematic prostate biopsy (SB). The overall age was 66 (60-72) years, and the overall PSA value was 8.22 (5.95-11.41) ng/ml. All patients underwent multiparametric magnetic resonance imaging (mpMRI), and PI-RADS v2.0 score was 3. Patients were divided into two mutually exclusive groups: non CsPCa group and CsPCa group. The differences of lesion location, laterality, focality and sequence parameters of mpMRI between the two groups were compared, and multivariate binary logistic regression was used to analyze the independent predictors of PI-RADS score 3 in patients with CsPCa.Results:Biopsy results showed 57 cases of prostate cancer, including 41 cases of CsPCa, and 76 cases of non-prostate cancer. The detection rate of prostate cancer was 46.62 %(57/133), and the detection rate of CsPCa was 30.83 %(41/133). There were 41 cases in CsPCa group and 92 cases in non CsPCa group. There was no significant difference between CsPCa group and non CsPCa group in age [66 (58-70) years vs. 66 (60-72) years], body mass index [24.22 (21.82-25.71) kg/m 2 vs. 23.71 (21.99-26.12) kg/m 2], PSA [9.39 (6.35-12.55) ng/ml vs. 7.67 (5.83-10.51) ng/ml], abnormal rate of rectal digital examination [21.95% (9/41) vs. 9.78% (9/92)] (all P > 0.05). There was significant difference in PSAD [0.40 (0.16-0.65) ng/ml 2 vs. 0.17 (0.12-0.24) ng/ml 2] ( P<0.05). In MRI, PI-RADS=3 lesions were mainly located in the transitional zone [46.62 %(62/133)]. In CsPCa group, MRI lesions were located in peripheral zone in 16 cases, transitional zone in 19 cases, and both areas in 6 cases. There were 16 cases on the right, 15 cases on the left and 10 cases on both sides. The lesions were diffused in 19 cases and localized in 22 cases. In the non CsPCa group, 41 lesions were located in the peripheral zone, 43 in the transitional zone, and 8 in both areas. There were 26 cases on the right, 35 cases on the left and 31 cases on both sides. The lesions were diffuse in 56 cases and localized in 36 cases. There was no significant difference in lesion location, side and diffusion degree between the two groups ( P> 0.05). Compared with the non CsPCa group, the positive rate of all MRI sequences in CsPCa group was higher (82.93% vs. 40.22%, P < 0.001), the positive rate of T2 weighted imaging (T2WI) was higher (92.68% vs. 75.00%, P = 0.018), the positive rate of diffusion weighted imaging (DWI) was higher (90.24% vs. 56.52%, P < 0.001), the maximum diameter was larger[(0.67(0.30-1.19)mm vs. 0.48(0.20-0.62)mm, P < 0.001], and the apparent diffusion coefficient (ADC) was lower[0.70(0.61-0.87) vs. 1.10(0.86-1.50), P < 0.001]. Concurrently, PSAD and lesion ADC were important predictors of CsPCa in logistic regression model [mean 10 fold cross validation AUC: 0.78(95% CI 0.65-0.88)]. Conclusions:Most of the MRI lesions in patients with PI-RADS 3 were located in the transitional zone, and the MRI lesions in CsPCa were more obvious and diffusion limited. PSAD and ADC values are independent predictors for the diagnosis of CsPCa in patients with PI-RADS score 3, and the log 2PSAD-ADC prediction model is helpful to find CsPCa from patients with PI-RADS score 3 and protect patients from unnecessary biopsy.

Objective:To explore the efficacy of single-plane bi-parameter magnetic resonance imaging (bpMRI) in the diagnosis of prostate cancer.Methods:The clinical data of 343 patients who underwent transperineal template prostate magnetic resonance-transrectal ultrasound (MRI-TRUS) cognitive fusion biopsy at the First Affiliated Hospital of Nanjing Medical University from January 2020 to July 2021 were retrospectively analyzed, with median age of [65.0(59.0, 72.0)] years, median body mass index (BMI) of [24.1(22.2, 25.6)]kg/m 2, median prostate volume (PV) of [41.7(29.1, 53.3)]ml, median PSA[6.9 (5.5, 8.4) ng/ml], median PSAD of[0.17(0.12, 0.22) ng/ml 2], and abnormal rate of digital rectal examination (DRE) [6.4%(22/343)]. All patients underwent initial biopsy and bi-parameter magnetic resonance imaging (bpMRI) examination before biopsy, and the images were interpreted using prostate image reporting and data system version 2.1 (PI-RADS v2.1). The detection rates of prostate cancer and clinically significant prostate cancer (csPCa) were compared between single-plane bpMRI and bpMRI. When PI-RADS≥3 score, MRI results were positive; when PI-RADS ≤2 score, MRI results were negative. Results:In the single-plane bpMRI group, 121 MRI results were negative and 222 were positive. Positive patients included 95 with PI-RADS 3 score, 94 with PI-RADS 4 score, and 33 with PI-RADS 5 score. In bpMRI group, 141 MRI results were negative and 202 were positive. Among the positive patients, 67 patients with PI-RADS 3 score, 102 patients with PI-RADS 4 score, and 33 patients with PI-RADS 5 score. The detection rates of single-plane bpMRI and bpMRI for prostate cancer were 22.3% (27/121) and 15.6% (22/141) in MRI negative cases[22.3% (27/121) and 15.6% (22/141), P=0.17], and PI-RADS scores with 3 points [35.8% (34/95) vs. 44.8% (30/67), P=0.25], 4 points [89.4% (84/94)vs. 90.2% (92/102), P=0.85] and 5 points [90.9% (30/33) vs. 93.9% (31/33), P=1.00] showed no significant difference in stratification. The detection rate of csPCa in the single-plane bpMRI group and bpMRI group was significantly different in the MRI negative cases [7.4% (9/121) and 2.1% (3/141), P=0.04]. PI-RADS scores with 3 points [22.1% (21/95) vs. 29.9% (20/67), P=0.27], 4 points [80.9% (76/94) vs. 79.4% (81/102), P=0.80] and 5 points [84.9% (28/33) vs. 90.9% (30/33), P=0.71] showed no significant difference in stratification. Conclusions:For those suspected of prostate cancer patients with PSA 4-10 ng/ml and PI-RADS score ≥3, single-plane bpMRI or bpMRI examination has the same efficacy in term of the detection rate of prostate cancer and csPCa.