Objective： To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood therapy for the treatment of diabetic mellitus erectile dysfunction. Methods： China National Knowledge Infrastructure(CNKI), Wanfang Data, VIP, Chinese Biomedical Database(CBM), PubMed, Cochrane Library, Embase and Web of Science were searched from inception until October 20th of 2024，for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction. Literature screening, quality evaluation, and data extraction were carried out in accordance with relevant standards. The software of RevMan5.4 was used for the analysis of publication bias. And meta-analysis was conducted to assess the impact of this therapy on IIEF-5, total effective rate, adverse reactions. The evidence levels according to the analysis results were evaluated. Results: Totally 19 RCTs were included, involving 1 612 patients. The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores (MD=3.59，95%CI［2.14，5.03］，P<0.01)，total effective rate (OR=4.30，95%CI［3.29，5.32］，P<0.000 01）. However, there was no statistically significant difference in the incidence of adverse reactions(OR=0.98，95%CI［0.48，2.01］，P=0.96) between the two groups. Conclusions： Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction. But considering the limited quantity of included studies, more high-quality studies still be needed to validate the therapeutic effect.
Humans ; Male ; Erectile Dysfunction/therapy* ; Randomized Controlled Trials as Topic ; Kidney ; Medicine, Chinese Traditional ; Diabetes Complications/therapy*

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective:To investigate beam distribution characteristics through a phantom with conventional or extended collimators designed based on conventional collimators in boron neutron capture therapy (BNCT).Methods:By Monte Carlo simulation, we calculated the neutron beam distributions along the beam direction with a conventional collimator, 5 cm-extended collimator, and 10 cm-extended collimator; calculated the irradiation time and average depth using 10 cm-extended collimators with no air gap comprised of lithium fluoride (LiF)+ polyethylene or boron carbide (B 4C)+ polyethylene at different mass ratios; and calculated the irradiation time, advantage depth, and off-axis dose with conventional or extended collimators at without air gap or certain air gaps. Results:For the 10 cm-extended collimator without air gap, the thermal neutron flux density, gamma ray dose rate, and fast neutron dose rate were highest, and their peaks were 1.0×10 9 n/(cm 2·s), 5.3 cGy/min, and 9.1 cGy/min, respectively. Collimators comprised of polyethylene and LiF were superior to those of polyethylene and B4C in advantage depth and irradiation time. For five types of collimators made of polyethylene and LiF, the combination of 20 wt% polyethylene and 80 wt% LiF exhibited the greatest advantage depth (8.7 cm), but with a longer irradiation time (20.5 minutes); and the combination of 80 wt% polyethylene and 20 wt% LiF achieved the shortest irradiation time (19.0 minutes), with an advantage depth of 8.5 cm. Compared with the conventional collimator, the use of 5 cm- and 10 cm-extended collimators reduced treatment time by 26.4% and 40.3%, respectively, with small changes in advantage depth; and for the same collimator, the off-axis dose increased with the increase in the air gap. Conclusions:The use of 5 cm- and 10 cm-extended collimators can increase neutron beam intensity and reduce irradiation time, with a small impact on advantage depth and off-axis dose, which can solve the problem of prolonged treatment time caused by an air gap between patient's tumor surface and the beam aperture when head and neck movement is limited. BNCT can be equipped with appropriate extended collimators according to actual clinical needs.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

Objective: To examine the radiomics model based on high-resolution T2WI and diffusion weighted imaging (DWI) in predicting microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer. Methods: From February 2016 to October 2020, 175 patients with stage Ⅱ and Ⅲ rectal cancer who met the inclusion criteria were retrospectively collected. There were 119 males and 56 females, aged (63.9±9.4) years (range: 37 to 85 years), including 152 patients with microsatellite stability and 23 patients with microsatellite instability. All patients were randomly divided into the training group (n=123) and the validation group (n=52) with a ratio of 7∶3. The region of interest was labeled on the T2WI and DWI images of each patient using the ITK-SNAP software, and PyRadiomics was used to extract seven kinds of radiomics features. After removing redundant features and normalizing features, the least absolute shrinkage and selection operation were used for feature selection. One clinical model, three radiomics models and one clinical-radiomics model were constructed in the training group based on a support vector machine. The area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to evaluate the performance of the models in the verification group. Results: Three clinical features (age, degree of tumor differentiation, and distance from the lower edge of the tumor to the anal edge) and six radiomics features (two DWI-related features and four T2WI-related features) most related to microsatellite status of rectal cancer patients were selected. The AUC of the clinical-radiomics model in the training group was 0.95. In the validation group, the AUC was 0.81, better than the clinical model (0.68, Z=0.71, P=0.04), and equivalent to the T2WI+DWI model (0.82, Z=0.21, P=0.83). Conclusions: Radiomic features based on preoperative T2WI and DWI were related to microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer and showed a high classification efficiency. The model based on the features provided a noninvasive and convenient tool for preoperative determination of microsatellite stability in rectal cancer patients.

Objective:To investigate the effect of ligand of numb-protein X1(LNX1)on the proliferation,invasion and migration of renal clear cell carcinoma cells and its underlying molecular mechanism. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the mRNA expression level of LNX1 in renal clear cell carcinoma tissues and its relationship with the prognosis of patients with renal clear cell carcinoma.LNX1 gene specific shRNA(shLNX1)was delivered into renal clear cell carcinoma cell lines 786-O and ACHN by lentiviral infection,and flag-LNX1 plasmid was delivered into 786-O and ACHN cells by transient transfection.CCK-8 assay and colony formation assay were used to assess the effects of LNX1 silencing or overexpression on the proliferation of 786-O and ACHN cells.Transwell assay was used to evaluate the effects of LNX1 silencing or overexpression on the invasion and migration of 786-O and ACHN cells.Bioinformatics analysis was used to screen the downstream target genes of LNX1.Western blotting was used to examine the effects of LNX1 silencing or overexpression on the expression level of T-lymphoma invasion and metastasis-inducing protein 1(TIAM1)as well as the expression levels of total and phosphorylated ERK(phospho-ERK,p-ERK)in the ERK signaling pathway downstream of TIAM1 in 786-O and ACHN cells.786-O and ACHN cells overexpressing LNX1 were treated with proteasome inhibitor MG132,and the protein expression level of TIAM1 was analyzed by Western blotting.Finally,myc-TIAM1 recombinant plasmid was transfected into LNX1-overexpressing cells.Then,the expression levels of proteins in the ERK signaling pathway and the abilities of proliferation,invasion and migration of 786-O and ACHN cells were examined by Western blotting,colony formation assay and Transwell assay,respectively. Results:The mRNA expression level of LNX1 in renal clear cell carcinoma tissue was decreased(P＜0.05)and was positively correlated with the survival time of patients with renal clear cell carcinoma(P＜0.001).LNX1-silencing 786-O and ACHN cells and LNX1-overexpressing 786-O and ACHN cells were constructed successfully.After LNX1 silencing,the proliferation,invasion and migration of 786-O and ACHN cells were significantly enhanced(all P＜0.05).After LNX1 overexpression,the abilities of proliferation,invasion and migration of 786-O and ACHN cells were significantly decreased(all P＜0.05).Bioinformatics analysis identified TIAM1 as a potential target of LNX1.After silencing LNX1,the protein expression levels of TIAM1 and p-ERK were significantly increased(all P＜0.05),while the expression level of ERK remained unchanged.After LNX1 overexpression,the protein expression levels of TIAM1 and p-ERKwere significantly decreased(all P＜0.01),while the expression level of ERK was unchanged.Treatment with proteasome inhibitor MG132 increased the protein expression level of TIAM1 in LNX1-overexpressing 786-O and ACHN cells(P＜0.01 and P＜0.001).After LNX1-overexpressing cells were transfected with myc-TIAM1 plasmid,the protein expression level of p-ERK was increased,the abilities of cell proliferation,invasion and migration were enhanced(all P＜0.05),and the expression level of ERK protein remained unchanged. Conclusion:LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by degrading TIAM1 which further regulates the phosphorylation of ERK.

Objective:To evaluate the accuracy and clinical outcomes of two different three-dimensional(3D) printed digital mandibular angle osteotomy templates.Methods:Female patients with a prominent mandibular angle(PMA) admitted to the same surgical team in the Friendship Plastic Surgery Hospital of Nanjing Medical University from March 2019 to July 2020 were selected as the research subjects. They were allocated into Group A and Group B alternately according to the order of admission. Group A was the conventional digital osteotomy template(CDOT) group, and Group B was the novel digital osteotomy template(NDOT) group. All patients underwent cone-beam computed tomography(CBCT) scan and 3D reconstruction before surgery. Preoperative CT data were imported into Mimics 19.0, and personalized mandibular angle osteotomy(MAO) line and digital osteotomy template(DOT) were designed according to patients’ conditions and requirements. In Group A, the DOTs were designed according to the part of mandibular angle to be removed(CDOT). And in Group B, the DOTs were designed according to to the part of reserved mandible(NDOT). The DOTs were created with a 3D printer. All patients were underwent bilateral MAO under the guidance of these DOTs through an intraoral approach. CBCT scan was also performed on all patients within 1 week after surgery, and incision healing, complications and lower facial contouring were observed. The mean time taken for positioning DOT and performing curved osteotomy, the volume of postoperative drainage on one side within 24 hours after surgery, and the deviations between the preoperative design and 3D reconstruction mode lower mandibular margin within 1 week after surgery were compared between the two groups.Results:A total of 20 female patients with PMA were included, including 10 patients in Group A, aged 20-31 years, with an average of 24.3±2.3 years. Group B consisted of 10 patients aged 22-30 years, with an average of 24.6±2.2 years. There was no significant difference in age between 2 groups ( P>0.05). All patients were successfully performed MAO without fracture, massive bleeding, infection and other complications, and the postoperative result were satisfactory. The mean time taken to position the DOT and perform MAO one side in Group A was (18.1±1.0) min, significantly longer than that in Group B (14.2±1.4) min ( P<0.05). The volume of postoperative drainage on one side within 24 hours in Group A and Group B was (107.9±12.5) ml and (112.1±13.8) ml, respectively ( P>0.05). The deviations between preoperative design and postoperative mandibular margin, at the anterior part was (2.7±1.2) mm in Group A, which was significantly larger than that of Group B[(1.6±0.9) mm]( P<0.05), the middle part deviation of Group A and B was (1.9±0.7) mm and (1.8±0.8) mm, respectively ( P>0.05), and the posterior part deviation of Group A was (2.8±1.1) mm, which was significantly higher than that of Group B (1.8±0.8 mm)( P<0.05). Conclusions:DOT assisted MAO can achieve accurate osteotomy and reduce the operative difficulty. The NDOT is easier to be located in the operation with more stable fixation, and the surgical efficiency and accuracy of osteotomy are higher than that of CDOT.

Objective:To evaluate the accuracy and clinical outcomes of two different three-dimensional(3D) printed digital mandibular angle osteotomy templates.Methods:Female patients with a prominent mandibular angle(PMA) admitted to the same surgical team in the Friendship Plastic Surgery Hospital of Nanjing Medical University from March 2019 to July 2020 were selected as the research subjects. They were allocated into Group A and Group B alternately according to the order of admission. Group A was the conventional digital osteotomy template(CDOT) group, and Group B was the novel digital osteotomy template(NDOT) group. All patients underwent cone-beam computed tomography(CBCT) scan and 3D reconstruction before surgery. Preoperative CT data were imported into Mimics 19.0, and personalized mandibular angle osteotomy(MAO) line and digital osteotomy template(DOT) were designed according to patients’ conditions and requirements. In Group A, the DOTs were designed according to the part of mandibular angle to be removed(CDOT). And in Group B, the DOTs were designed according to to the part of reserved mandible(NDOT). The DOTs were created with a 3D printer. All patients were underwent bilateral MAO under the guidance of these DOTs through an intraoral approach. CBCT scan was also performed on all patients within 1 week after surgery, and incision healing, complications and lower facial contouring were observed. The mean time taken for positioning DOT and performing curved osteotomy, the volume of postoperative drainage on one side within 24 hours after surgery, and the deviations between the preoperative design and 3D reconstruction mode lower mandibular margin within 1 week after surgery were compared between the two groups.Results:A total of 20 female patients with PMA were included, including 10 patients in Group A, aged 20-31 years, with an average of 24.3±2.3 years. Group B consisted of 10 patients aged 22-30 years, with an average of 24.6±2.2 years. There was no significant difference in age between 2 groups ( P>0.05). All patients were successfully performed MAO without fracture, massive bleeding, infection and other complications, and the postoperative result were satisfactory. The mean time taken to position the DOT and perform MAO one side in Group A was (18.1±1.0) min, significantly longer than that in Group B (14.2±1.4) min ( P<0.05). The volume of postoperative drainage on one side within 24 hours in Group A and Group B was (107.9±12.5) ml and (112.1±13.8) ml, respectively ( P>0.05). The deviations between preoperative design and postoperative mandibular margin, at the anterior part was (2.7±1.2) mm in Group A, which was significantly larger than that of Group B[(1.6±0.9) mm]( P<0.05), the middle part deviation of Group A and B was (1.9±0.7) mm and (1.8±0.8) mm, respectively ( P>0.05), and the posterior part deviation of Group A was (2.8±1.1) mm, which was significantly higher than that of Group B (1.8±0.8 mm)( P<0.05). Conclusions:DOT assisted MAO can achieve accurate osteotomy and reduce the operative difficulty. The NDOT is easier to be located in the operation with more stable fixation, and the surgical efficiency and accuracy of osteotomy are higher than that of CDOT.

Objective To investigate the effects of Smad7 knock down by lentivirus on rat cardiac fibroblasts proliferation, migration, cell differentiation and collagen secretion in vitro. Methods The primary cardiac fibroblasts were separated from the hearts of ten SD rats and identified by immunohistochemical method. The lentivirus transfection knocked down the expresson of Smad7 in cardiac fibroblasts, Western blotting was used to detect the efficiency of Smad7 knock down by lentivirus. The proliferation of cardiac fibroblasts was quantified by real-time unlabeled cell analyzer. Cell migration was evaluted by cell wound scratch assay. Western blotting was used to detect expression of α-smooth muscle actin（α-SMA） and collagen Ⅰ（Col Ⅰ）. Results Myocardial fibroblasts were successfully cultured and identified by immunocytochemical methods. The multiplicity of infection（MOI） that lentivirus transduction of myocardial fibroblasts was 100. After lentivirus transduction, 88.33% myocardial fibroblasts expressed green fluorescent protein, showed that the lentivirus could significantly reduce the protein expression of Smad7. Smad7 deficiency decreased the proliferation and migration of cardiac fibroblasts, increased the protein expression of α-SMA and decreased collagen secretion. The results indicated that Smad7 deficiency significantly down-regulated the proliferation and migration of cardiac fibroblasts, increased α-SMA protein expression and reduced ColⅠ protein expression. Conclusion Smad7 deficiency can significantly change the cardiac fibroblasts function, that is related to the pathological mechanism that lead to myocardial fibrosis

Direct-acting antivirals (DAAs) can strongly inhibit the replication of hepatitis C virus (HCV) and effectively clear the infection, but it may cause hepatitis B virus (HBV) reactivation, leading to severe liver damage and fulminate hepatitis in patients with HCV/HBV coinfection. In this review, we summarized the different replication process of HCV and HBV in infected hepatocytes and consequent innate immune response, and then discussed the molecular mechanism and clinical significance of HBV reactivation, and put forward the clinical precaution.
Humans ; Hepatitis B virus ; Hepacivirus ; Antiviral Agents/pharmacology* ; Hepatitis C, Chronic/drug therapy* ; Virus Activation ; Hepatitis C/drug therapy* ; Coinfection/drug therapy* ; Hepatitis B/drug therapy*