Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.

[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

【Objective】 To investigate the efficacy of robot-assisted single-port laparoscopic transvaginal vesicovaginal fistula repair. 【Methods】 The clinical data of 3 patients with high vesicovaginal fistula treated during Jun.2020 and Jun.2021 were retrospectively analyzed. 【Results】 All operations were completed successfully, with no conversion to other surgical methods. Operation time: 98 min, 104 min and 115 min; Intraoperative bleeding volume: 15 mL, 20 mL and 22 mL; Postoperative hospital stay was 2 days. The catheter was removed after 1-month follow-up, and the patients had no bleeding, urine leakage, infection or other complications. There was no recurrence of urine leakage at the end of 12-month follow-up. 【Conclusion】 Robot-assisted single-port laparoscopic transvaginal vesicovaginal fistula repair has the advantages of fine suture and minor damage, which can be an effective treatment of vesicovaginal fistula.

To investigate the changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute normovolemic hemodiluti-on and its influence on the depth of anesthesia, muscle relaxant effect and blood drug concentration after reinfusion. METHODS: Forty patients of both sexes, aged 20-60 yr, American Society of Anesthesiologists physical status or Ⅱ, hemoglobin (Hb) >120 g / L, hematocrit (Hct) >35%, undergoing eletive multilevel spinal surgery were included, were divided into 2 groups (n=20 each) using a random number table. ANH group (group A): ANH was performed after stable induction of anesthesia, the target Hct value was 28%-30%, and autologous blood was reinfused after the main operation steps. Control group (group C): routine transfusion and infusion treatment. The bispectral index (BIS) and Train-of-Four stimulation (TOF) were observed and recorded at the stable induction of anesthesia (T1), 30 minutes of stable induction (T2), the end of operation (T3), 30 minutes after the end of the operation (T4), 1 hour after the end of the operation (T5) and 2 hours after the end of the operation (T6). The concentrations of propofol and cisatracurium besylate in plasma at T1-T6, stored blood at 1 h (TS1), 2 h (TS2), and before reinfusion (TS3) were detected by Liquid Chromatography-tandem Mass Spectrometry. The extubation time and recovery score at T4-6 hours were recorded. RESULTS: There was no significant difference in propofol between the two groups at each time point (P > 0.05). The plasma concentration of cisatracurium besylate in group A was higher than that in group C at T3 (P<0.05). The concentration of two kinds of anesthetic drugs in blood samples decreased slightly with time,but there was no significant difference between groups (P>0.05). The BIS value at T4 and TOF value at T3 in group A were significantly lower than those in group C. The recovery score of group A was lower than that of group C at T4 (P<0.05). There was no significant difference in extubation time (P>0.05). CONCLUSION: The plasma concentrations of propofol and cisatracurium besylate were basically unchanged during the in vitro isolation of ANH autologous blood. The plasma concentrations of cisatracurium besylate were only temporarily affected after the main operation steps, but the postoperative muscle relaxation recovery and recovery quality were not significantly affected.

Objective To investigate the intervention effect of Xuanfuhua decoction on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat, high-fructose, and high-cholesterol diet. Methods A total of 32 male C57/BL6J mice were randomly divided into normal group, model group, Xuanfuhua decoction group, and obeticholic acid group, with 8 mice in each group. Since week 24 of modeling using high-fat, high-fructose, and high-cholesterol diet, each group was given the corresponding drug for intervention at a dose of 14.19 g/kg by gavage for the Xuanfuhua decoction group and 10 mg/kg by gavage for the obeticholic acid group and a volume of 20 mL/kg for gavage, once a day for 6 consecutive weeks. HE staining, oil red O staining, Sirius Red staining, and Masson staining were used to observe the pathological changes, lipid deposition, and collagen deposition of liver tissue; related kits were used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and glucose, as well as the content of TG and hydroxyproline (Hyp) in liver tissue; quantitative real-time PCR was used to measure the expression of genes associated with lipid metabolism, inflammation, and fibrosis in liver tissue; immunohistochemical staining was used to observe the positive expression of F4/80 and α-SMA in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in body weight, liver wet weight, and serum levels of AST, ALT, TC, TG, LDL-C and glucose (all P < 0.01). HE staining showed hepatocyte steatosis, a large number of fat vacuoles, hepatocyte ballooning degeneration, and inflammatory cell infiltration in liver tissue of the mice in the model group, and the model group had a significant increase in NAFLD activity score (NAS) compared with the normal group ( P < 0.01). Oil red O staining showed the deposition of a large number of red lipid droplets with different sizes in hepatocytes of the mice in the model group, and compared with the normal group, the model group had significant increases in the area percentage of oil red O staining and the content of TG in the liver ( P < 0.01). Sirius Red staining and Masson staining showed significant collagen fiber hyperplasia in the perisinusoidal area, the central vein, and the portal area in the model group, and the model group had a significant increase in the content of Hyp in liver tissue compared with the normal group ( P < 0.05). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the serum levels of AST, ALT, TC, TG, LDL-C, and glucose (all P < 0.05), significant improvements in hepatic steatosis, inflammatory infiltration, lipid droplet deposition, and collagen fiber hyperplasia, and significant reductions in NAS score, area percentage of oil red O staining, and content of TG and Hyp in the liver (all P < 0.05). Compared with the normal group, the model group had significant increases in the mRNA expression levels of lipid metabolism-related genes (SREBP-1c, FASN, SCD-1, PPAR-γ, and CD36), inflammation-related genes (F4/80, TNF-α, CCL2, and CD11b), and the fibrosis-related gene α-SMA (all P < 0.05), and immunohistochemical staining showed significant increases in the positive expression of F4/80 and α-SMA ( P < 0.01). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the mRNA expression levels of SREBP-1c, FASN, SCD-1, PPAR-γ, CD36, F4/80, TNF-α, CCL2, CD11b, and α-SMA in liver tissue (all P < 0.05), and immunohistochemical staining showed significant reductions in the positive expression of F4/80 and α-SMA ( P < 0.01). Conclusion Xuanfuhua decoction has a good intervention effect on mice with NASH induced by high fat, high fructose, and high-cholesterol diet and can significantly inhibit hepatic lipid deposition, inflammatory response, and liver fibrosis.

BACKGROUND: To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in regulating sepsis-associated acute kidney injury (S-AKI). METHODS: A total of 96 mice were randomly divided into the control group, control+MANF group, S-AKI group, and S-AKI+MANF group. The S-AKI model was established by injecting lipopolysaccharide (LPS) at 10 mg/kg intraperitoneally. MANF (200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups. An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups. Serum and kidney tissue samples were obtained for biochemical analysis. Western blotting was used to detect the protein expression of MANF in the kidney, and enzyme-linked immunosorbent assay (ELISA) was used to determine expression of MANF in the serum, pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]). Serum creatinine (SCr), and blood urea nitrogen (BUN) were examined using an automatic biochemical analyzer. In addition, the kidney tissue was observed for pathological changes by hematoxylin-eosin staining. The comparison between two groups was performed by unpaired Student’s t-test, and statistics among multiple groups were carried out using Tukey’s post hoc test following one-way analysis of variance (ANOVA). A P-value <0.05 was considered statistically significant. RESULTS: At the early stage of S-AKI, MANF in the kidney tissue was up-regulated, but with the development of the disease, it was down-regulated. Renal function was worsened in the S-AKI group, and TNF-α and IL-6 were elevated. The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney. The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group. CONCLUSION: MANF treatment may significantly alleviate renal injury, reduce the inflammatory response, and alleviate or reverse kidney tissue damage. MANF may have a protective effect on S-AKI, suggesting a potential treatment for S-AKI.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Kabuki syndrome (MIM 147920) is an autosomal dominant rare disease featured with multiple malformations and mental retardation. The main clinical manifestations of Kabuki syndrome are characteristic facial features, skeletal abnormalities, dermatoglyphic abnormalities, postpartum growth retardation, mild to moderate mental retardation, as well as other structural and functional abnormalities that may involve multiple systems. The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation. Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients, few prenatal diagnosis cases of Kabuki syndrome had been reported, which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis. This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites, thickening of local skin, and cardiac abnormalities. We ruled out intrauterine infection, thalassemia, and chromosome abnormality by corresponding tests. Finally, trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g > A (p.r5214h) in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome. This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites. Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities, and a multidisciplinary team is necessary for providing pregnancy guidance to patients.

Kabuki syndrome (MIM 147920) is an autosomal dominant rare disease featured with multiple malformations and mental retardation. The main clinical manifestations of Kabuki syndrome are characteristic facial features, skeletal abnormalities, dermatoglyphic abnormalities, postpartum growth retardation, mild to moderate mental retardation, as well as other structural and functional abnormalities that may involve multiple systems. The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation. Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients, few prenatal diagnosis cases of Kabuki syndrome had been reported, which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis. This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites, thickening of local skin, and cardiac abnormalities. We ruled out intrauterine infection, thalassemia, and chromosome abnormality by corresponding tests. Finally, trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g > A (p.r5214h) in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome. This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites. Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities, and a multidisciplinary team is necessary for providing pregnancy guidance to patients.

Patients with malignant tumour often require massive transfusion. Intraoperative cell salvage(IOCS) was initially limited in cancer surgery by concerns about the possibility of dissemination of tumor cells into circulation. However, as supportive literature concerning IOCS research and application in cancer surgery are increasing, it is necessary to reassess the perioperative application of IOCS in patients with malignancy. This review summarizes the application, risks and value of IOCS during cancer operations.