OBJECTIVE: To evaluate the impact of sutureless approach to the dorsal venous complex (DVC) combined with robotic-assisted laparoscopic prostatectomy on sexual function of patients with prostatic cancer. METHODS: This study included 114 prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital from January 2021 to January 2024. The patients were randomly divided into a control group (n=57) and an observation group (n=57). The control group received conventional "figure-of-eight" suture ligation of the dorsal venous complex (DVC), while the observation group underwent direct DVC transection using monopolar electrocautery scissors after increasing pneumoperitoneum pressure.Surgical duration, intraoperative blood loss, positive surgical margin rates, and positive apical margin rates were recorded. The continence rates and rates of morning erections at 1, 3 and 6 months after the operation were compared between groups. Sexual function was assessed pre-operatively and at 6 months post-operation by using the IIEF-5 and PEDT. RESULTS: The operative time in the observation group was significantly longer than that in the control group (［115.71 ± 19.42］ min vs ［103.42 ± 12.78］ min， P<0.05). While no significant differences were observed in intraoperative blood loss, positive surgical margin rate, or positive apical margin rate between the two groups (P>0.05). At 3 and 6 months after the operation, the observation group exhibited higher urinary continence rates and morning erection recovery rates compared to the control group （P<0.05). Furthermore, at 6 months postoperatively, the observation group demonstrated significantly higher IIEF-5 scores and lower PEDT scores than those of control group(P<0.05). CONCLUSION The use of a sutureless DVC technique in robotic-assisted laparoscopic radical prostatectomy protects the post-operative sexual function in patients.
Humans ; Male ; Prostatectomy/methods* ; Laparoscopy/methods* ; Prostatic Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Middle Aged ; Operative Time ; Aged

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective:To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID).Methods:Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People′s Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants.Results:A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c. 676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c. 184_185delAC variant of the BTK gene, and the c. 472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c. 184_185delAC and CYBB: c. 472A>T variants were classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c. 184_185 position of the BTK gene, the c. 472 position of the CYBB gene, and the c. 676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. Conclusion:WES is an important tool to infer and analyze the carryier status for couples who had given births to children died of PID and improve the positive detection rate.

Objective To investigate the role and underlying mechanism of miR-15b-5p on hypoxia/reoxygenation(H/R)induced human renal tubular epithelial cell(HK-2)injury by targeting forkhead box O1(FOXO1).Methods HK-2 cells in the log growth phase were set up as follows:(1)control group(normal culture)and H/R group(H/R induced culture).The expressions of miR-15b-5p and FOXO1 mRNA were detected using qRT-PCR,and the protein expression of FOXO1 was detected using Western blotting.(2)Control group(normal culture),H/R group(H/R induced culture),H/R+mimic control group(cells transfected with mimic control then induced by H/R),H/R+miR-15b-5p mimic group(cells transfected with miR-15b-5p mimic then induced by H/R),H/R+miR-15b-5p mimic+OE-NC group(cells co-transfected with miR-15b-5p mimic and OE-NC plasmid,then induced by H/R),and H/R+miR-15b-5p mimic+OE-FOXO1 group(cells co-transfected with miR-15b-5p mimic and FOXO1 overexpression plasmid,then induced by H/R).The expression of miR-15b-5p was detected using qRT-PCR,and the protein expressions of FOXO1,cleaved caspase-3,Bax,and Bcl-2 were detected using Western blotting.CCK-8 assay was used to detect cell viability.Cell apoptosis was measured by the TUNEL method.(3)Control group(normal culture),H/R group(H/R induced culture),H/R+miR-15b-5p mimic group(cells transfected with miR-15b-5p mimic then induced by H/R),and H/R+miR-15b-5p mimic+OE-FOXO1 group(cells co-transfected with miR-15b-5p mimic and FOXO1 overexpression plasmid,then induced by H/R).The protein expressions of LC3,p62 and Beclin1 were detected using Western blotting.LC3 immunofluorescence was used to detect the cell autophagy.The target reaction between miR-15b-5p and FOXO1 was assessed using dual luciferase reporting assay.Results Under an inverted microscope,it was observed that the control group had a higher number of cells,most of which were in a typical cobblestone shape and grew in a cobblestone-like manner;most of the cells in the H/R group contracted and became round,with a significant decrease in the number of adherent cells.In H/R-induced HK-2 cells,miR-15b-5p was significantly down-regulated,while miRNA and protein expression of FOXO1 was up-regulated(P<0.05).Luciferase assay results showed that miR-15b-5p directly targeted the 3'-UTR of FOXO1.Overexpression of miR-15b-5p increased cell viability,reduced cell apoptosis,and decreased autophagy in H/R-induced HK-2 cells(P<0.05).Compared with H/R+miR-15b-5p mimic group,the viability of HK-2 cells was decreased,the apoptosis and autophagy level were increased in H/R+miR-15b-5p mimic+OE-FOXO1 group(P<0.05).Conclusion miR-15b-5p inhibited autophagy and alleviated H/R-induced HK-2 cell injury by targeting FOXO1.

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.

Objective:To analyze the clinical phenotype and genetic characteristics of probands in 3 pedigrees of complex hereditary spastic paraplegia type 5 (HSP5) who developed symptoms during childhood, and the genetic diagnostic methods of HSP5 to improve the diagnosis and differential diagnosis of this disease.Methods:The clinical data of 3 HSP5 families admitted to Henan Provincial People′s Hospital from June 2020 to January 2023 were collected. Whole exome sequencing (WES) was performed on the patients to analyze phenotype-related single nucleotide variation (SNV) and small fragment insertion/deletion (INDEL) variation. At the same time, the sequencing data were used to analyze the dynamic mutation regions of specific genes.Results:The probands in the 3 families had complex HSP: the proband in family 1 showed weakness of both lower limbs, urgency of urination and ataxia; the proband in family 2 showed slightly lower intelligence, weakness of both lower limbs, dysarthria, and brain magnetic resonance imaging showed white matter lesions; the proband in family 3 showed muscle weakness, spasm, frequent urination and ataxia of both lower limbs. The sequencing results showed that the CYP7B1 gene c.1171G>T (paternal) and c.1249C>T (maternal) compound heterozygous mutations were found in proband 1 and his younger brother. The CYP7B1 gene c.334C>T (paternal) and c.259+2T>C (maternal) compound heterozygous mutations were found in proband 2 and her younger sister. The CYP7B1 gene c.334C>T (paternal) and c.1082G>A (maternal) compound heterozygous mutations were found in proband 3. And c.1171G>T was a new variant that had not been reported before. Dynamic mutation analysis showed that the numbers of CAG repeats of ATXN1/2/3/6/7/8/12, DRPLA, TBP genes were within the normal range. According to the clinical manifestations and genetic examination results of the children in the 3 pedigrees, the diagnosis of HSP5 was clear. Conclusions:The 3 families in the study all had complex HSP5 caused by compound heterozygous mutations of the CYP7B1 gene. WES can analyze SNV, INDEL and dynamic mutations simultaneously to make the maximum clear diagnosis and can be used as an effective detection method for HSP5.

OBJECTIVE: To explore clinical effect of Zero-profile intervertebral fusion with cage-titanium plate in treating multilevel cervical spondylotic myelopathy. METHODS: From January 2016 to January 2020, 107 patients with multisegmental cervical spondylotic myelopathy treated by surgery were retrospectively analyzed and divided into Hybrid group and control group according to different surgical methods. There were 54 patients in Hybrid group, including 42 males and 12 females, aged from 33 to 77 years old with an average of (57.3±9.5) years old;20 patients with C₃-C₆, 27 patients with C₄-C₇ and 7 patients with C₃-C₇;Zero-profile intervertebral fusion with cage-titanium plate internal fixation was performed. There were 53 patients in control group, including 34 males and 19 females;aged from 36 to 79 years old with an average of (57.8±8.9) years old;17 patients with C₃-C₆, 27 patients with C₄-C₇, and 9 patients with C₃-C₇;titanium plate interbody fusion fixation was performed. Operation time, blood loss and complications between two groups were compared, visual analogue scale (VAS), Japanese Orthopedic Association (JOA) scores and neck disability index (NDI) were used to assess recovery of clinical symptoms;cervical lordosis (CL), cervical sagittal vertical axis (C-SVA), and T₁ slope (T₁S) were measured and compared to evaluate cervical sagittal plane parameters. RESULTS: All patients were followed up, Hybrid group was followed up for 24 to 64 months with an average of (31.7±18.4) months, and control group was followed up for 24 to 65 months with an average of (32.6±15.8) months. There was no significant difference in follow-up time between two groups (P>0.05). Operation time and blood loss in Hybrid group were less than those in control group (P<0.05). VAS, JOA score and NDI were significantly improved between two groups at the lastest follow-up (P<0.05). There were no significant difference in VAS, JOA and NDI scores between two groups before and after operation (P>0.05). CL in both two groups at 3 months and the latest follow-up after operation were significantly improved than those before operation (P<0.05), there were no significant difference between two groups in T1S and C-SVA before and after operation (P>0.05). Postoperative dysphagia occurred in 2 patients in Hybrid group and 9 patients in control group, and had statistically difference in the incidence of dysphagia between two groups (χ²=5.112, P=0.024). During the follow-up, there were no complications such as loosening, displacement or fracture of internal fixation between two groups. CONCLUSION Compared with titanium plate interbody fusion, Zero-profile intervertebral fusion combined with cage-titanium plate for the treatment of multilevel cervical spondylotic myelopathy could shorten surgical time and blood loss, reduce surgical trauma and postoperative swallowing difficulties, and is conducive to early and rapid recovery.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/instrumentation* ; Bone Plates ; Titanium ; Aged ; Spondylosis/surgery* ; Adult ; Cervical Vertebrae/surgery* ; Retrospective Studies ; Spinal Cord Diseases/surgery*

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.
Humans ; Infant ; Male ; Acute Disease ; Ascites ; Cholesterol ; Hyperlipoproteinemia Type I/genetics* ; Hyperlipoproteinemias ; Lipoprotein Lipase/genetics* ; Pancreatitis ; Triglycerides

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.