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*

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Objective    To explore the risk factors and predictive value of acute kidney injury (AKI) after total aortic arch replacement. Methods    The clinical data of patients undergoing total aortic arch replacement in our hospital from January 2018 to June 2019 were retrospectively analyzed, and patients receiving preoperative renal replacement therapy and missing creatinine values were excluded. According to whether postoperative AKI occurred, patients were divided into an AKI group and a control group. The univariate and multivariate analyses (logistic regression) were used to explore the independent risk factors of AKI. The receiver operating characteristic curve was used to analyze the significant factors in predicting the occurrence of AKI after total aortic arch replacement. Results    A total of 162 patients were included in the study, including 135 (83.3%) males and 27 (16.7%) females, with an average age of 52.61±9.90 years (range: 22 to 73 years). The incidence of AKI was 68.5% (n=111). The results of univariate and multivariate analyses showed that the postoperative serum cystatin C level (OR=76.145, 95%CI 15.575-372.260, P<0.01) was an independent risk factor for AKI after total aortic arch replacement. When its cut-off value was above 1.08 mg/L, the specificity for predicting postoperative AKI was 70.59%, and the sensitivity was 85.59%. Conclusion    The postoperative cystatin C level is an independent risk factor for AKI after total aortic arch replacement and has predictive value.

Recently, the incidence rate of infertility has been increasing year by year. Lesions of the female reproductive system are the most important causes of infertility, such as premature ovarian failure, polycystic ovary syndrome, pelvic inflammatory disease, endometriosis, recurrent abortion, etc. However, the specific pathogenesis of infertility needs to be further studied. Gene editing is a technical method to change the sequence of deoxyribonucleic acid (DNA) in biological cells, which is an indispensable tool for studying gene function and disease pathogenesis. In this research, we review the recent progress in studying the pathogenesis of female infertility related diseases through gene editing technology, so as to explore a new direction for the clinical diagnosis and treatment of infertility.

Objective:To observe the clinical efficacy and safety of recombinant human granulocyte macrophage stimulating factor (rhGM-CSF) combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 39 patients with newly diagnosed DLBCL treated with rhGM-CSF combined with R-CHOP regimen, and 39 patients with newly diagnosed DLBCL treated with R-CHOP regimen in Naval Medical University (Changhai Hospital) from February 2017 to November 2019 were retrospectively analyzed. The total response rate (ORR), remission rate (CR) rate, overall survival (OS), progression-free survival (PFS) and adverse reactions of both groups were compared.Results:In rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group, ORR was 87.2% (34/39) and 82.1% (32/39), respectively, and the difference was statistically significant ( χ2 = 0.394, P = 0.53); CR rate was 71.8% (28/39) and 56.4% (22/39), respectively, and the difference was statistically significant ( χ2 = 2.006, P = 0.157). Until the last follow up on September 19, 2020, 32 patients survived and 7 patients died in rhGM-CSF combined with R-CHOP regimen group, of which 1 case died of bowel cancer, and the primary disease was still in CR. In the R-CHOP regimen group, 32 survived and 7 died. The 2-year OS rates of the two groups were 82.5% and 73.9%, respectively ( χ2 = 0.038, P = 0.845); the 2-year PFS rates of the two groups were 67.1% and 55.2%, respectively ( χ2 = 0.457, P = 0.499). Subgroup analysis results showed that there were no statistically significant differences in CR rates among germinal center B-cell (GCB) and non-GCB subgroups, Lugano stage Ⅰ-Ⅱ and Lugano stage Ⅲ-Ⅳ subgroups, aged <60 years and aged ≥60 years subgroups in rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group (all P > 0.05). The major adverse reactions included bone marrow suppression and its inducible infections. There were no significant differences in the incidence of grade 3-4 hematological adverse reactions and infections between the two groups (all P > 0.05). All patients safely went through bone marrow suppression after support treatments without treatment-related deaths. Conclusions:rhGM-CSF combined with R-CHOP regimen is safe and effective in treatment of newly diagnosed DLBCL.

Objective    To explore the correlation between perioperative blood transfusion and acute kidney injury (AKI) after heart transplantation. Methods    A retrospective study was performed on 67 patients who underwent heart transplantation in the Department of Cardiac Surgery, Guangdong Provincial People's Hospital from January 2016 to December 2018, and finally 63 patients were included according to the exclusion criteria. There were 53 males and 10 females with an average age of 44.3±12.9 years. Twenty patients who adopted continuous renal replacement therapy (CRRT) after heart transplantation were divided into a RT group and the other 43 patients who did not use CRRT were divided into a non-RT group. Baseline characteristics, perioperative blood transfusion data and clinical prognosis were compared between the two groups. Results    The preoperative baseline characteristics of the two groups were basically the same. There were significant differences in perioperative infusion of red blood cells and plasma, postoperative 24 h bleeding and re-exploration (P<0.05) between the two groups. The area under the receiver operating characteristic (ROC) curve was 0.923 (95%CI 0.852 to 0.995, P<0.001). The ROC curve showed that perioperative infusion of red blood cells more than 18 mL/kg would increase the incidence of AKI after heart transplantation. Conclusion    Perioperative blood transfusion is closely related to AKI after heart transplantation. The more blood transfusion is in clinics, the higher incidence of renal injury is and the worse prognosis is. It is suggested that various blood-saving measures can be carried out.

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR₁) and negative minimal residual disease (MRD^-) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR₁/MRD^- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR₁/MRD^- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion Allo-HSCT for candidate patients without further consolidation when CR₁/MRD^- was attained was feasible.

Objective:It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer.Methods:The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools.Results:A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77, P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion:The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.

Objective:It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer.Methods:The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools.Results:A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77, P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion:The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.

Objective:To evaluate the clinicopathologic characteristics and outcomes of HIV-negative plasmablastic lymphoma (PBL) .Methods:Medical records of 15 patients diagnosed with HIV-negative PBL in Changhai Hospital between January 2013 and August 2019 were reviewed, and clinicopathologic characteristics and outcomes were analyzed.Results:Median age was 59 years (range: 17-69) . All patients had extranodal involvement. According to the Cotswolds-modified Ann Arbor staging system, 1 (6.7%) , 2 (13.3%) , 3 (20.0%) , and 9 (60.0%) patients were classified as at Ⅰ,Ⅱ,Ⅲ and Ⅳ, respectively. Plasmablast and immunoblast proliferations were typical manifestations of PBL. Immunohistochemical staining showed tumor cells were diffusely positive for plasma cell markers CD38, CD138, and Mum-1, while negative for B cell markers CD20, CD10, PAX-5, and BCL-6. Median Ki-67 index was 80% (70%-90%) . Epstein-Barr virus-encoded RNA (EBER) expression was detected in 3 patients, and 1 of them was positive. All patients received chemotherapy, 80% combined with bortezomib as the first line, and responses were observed in 8 patients (6 complete and 2 partial responses) . Median progression-free survival (PFS) and overall survival (OS) were 6.8 (95% CI 2.5-11.1) months and 17.9 (95% CI 5.6-30.2) months, the 3-year PFS and OS rates were 21.2% (95% CI 1.4%-56.8%) and 38.5% (95% CI 12.0%-65.0%) , respectively. Conclusion:HIV-negative PBL with high invasiveness is extremely prone to extranodal involvement and most patients were at the advanced stage. Patients receiving an intensive therapy combined with bortezomib and bridged autologous stem cell transplantation may improve long-time survival.