Prostate cancer (PCa) is one of the most common cancer among men worldwide.With the continuous development of genomics technology，a large number of studies have confirmed that different types of gene mutations affect the clinical manifestations，progression and prognosis of PCa.Tumor genomics research can go deep into the gene level to explore the causes of PCa，explore possible biomarkers，and identify potential therapeutic targets.This paper discusses the development and application of whole-exome sequencing (WES) in prostate cancer，including DNA damage repair (DDR) related gene mutations，homologous recombination repair (HRR) key gene mutations，other HRR related gene mutations，mismatch repair related gene mutations and other gene mutations，differences in PCa gene mutations between different races，and differences in localized PCa and metastatic PCa gene mutations，so as to provide reference for the stratified diagnosis and individualized treatment of PCa.

【Objective】 To identify the risk factors of patients of bone metastatic prostate cancer with high tumor load progressed to castration resistant prostate cancer (CRPC), establish a nomogram prediction model and evaluate its consistency and accuracy. 【Methods】 A total of 164 patients diagnosed by puncture and imaging during 2012 and 2022 were included.The general characteristics were analyzed with IBM SPSS software; the variables were screened with Cox regression; the multivariate risk factors with P<0.05 were included in the nomogram prediction model.The consistency and prediction accuracy of the model were evaluated with C-index, receiver operating characteristic (ROC) curve and calibration chart. 【Results】 In univariate analysis, initial prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), Gleason score, T stage, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were correlated with CRPC (P<0.05).Multivariate analysis showed that initial PSA, Gleason score, T stage, ALP and LDH were independent risk factors of CRPC (P<0.05).Based on the above five risk factors, a nomogram prediction model was constructed.The C-index was 0.801, the area under ROC curve (AUC) of 1-year progression-free survival (PFS) was 0.701 (0.608-0.794), and the AUC of 2-year PFS was 0.857 (0.767-0.947).The calibration chart showed that the prediction probability of the model was in good agreement with the actual probability. 【Conclusion】 Initial PSA, Gleason score, T stage, ALP and LDH are independent risk factors of CRPC.The predictive model may be an effective tool for the initial diagnosis of high tumor load bone metastatic prostate cancer, but more data are needed for internal and external validation.

Objective To investigate the relationship between initial serum testosterone level and aggressive characteristics,progression and prognosis of metastatic prostate cancer(mPCa).Methods The clinical data of 302 mPCa patients diagnosed with biopsy and auxiliary examinations at the First Affiliated Hospital of Xinjiang Medical University during Aug.2010 and Aug.2022 were retrospectively analyzed,including 148 cases in the serum testosterone low level group(≤12 nmol/L)and 154 in the normal level group(＞12 nmol/L).The independent risk factors associated with aggressive features were analyzed with multifactorial logistic regression,survival was determined with Kaplan-Meier method,the independent risk factors affecting progression and prognosis were identified with multifactorial Cox regression modeling,and the value of initial serum testosterone level in predicting the progression and survival was assessed with receiver operating characteristic(ROC)curve.Results The low level group had a higher proportion of Gleason score ≥8,T stage＞3,initial prostate-specific antigen(PSA)＞200 ng/mL,high tumor load,visceral metastasis,PSA≥ 0.2 ng/mL after 6 months of treatment,and higher body mass index(BMI),but the PSA decline rate after 6 months of treatment was lower than that in the normal level group(P＜0.05).Multifactorial logistic regression showed that initial serum testosterone level＞12 nmol/L was a protective factor for high tumor load(OR=0.137,95％CI:0.070-0.265,P＜0.001),Gleason score ≥8(OR=0.371,95％CI:0.184-0.750,P=0.006)and visceral metastasis(OR=0.337,95％CI:0.175-0.652,P=0.001).The median progression-free survival was shorter in the low level group than in the normal level group(15 months vs.20 months,P＜0.001),and the median overall survival time was also shorter(45 months vs.86 months,P＜0.001).Multifactorial Cox regression analysis showed that Gleason score ≥8,high tumor load,PSA value at 6 months of treatment,and PSA decline rate were independent influencing factors for progression to castration resistant prostate cancer(CRPC)(P＜0.05).The risk of death in patients with high tumor load was 2.510 times higher than that of patients with low tumor load(95％CI:1.555-4.051,P＜0.001).ROC curves showed that initial serum testosterone level could predict the risk of progression to CRPC(AUC:0.645)and survival(AUC:0.595).Conclusion Low level initial serum testosterone is associated with an aggressive profile and poor prognosis of mPCa,and can predict the risk of progression and survival status of mPCa patients.

[Objective] To explore the clinical efficacy and feasibility of blue laser transurethral incision of prostate (BLTUIP) in the treatment of small volume (≤30 mL) benign prostatic hyperplasia (BPH). [Methods] The clinical data of 34 BPH patients treated with BLTUIP in the First Affiliated Hospital of Xinjiang Medical University during Mar.and Oct.2023 were retrospectively analyzed.The operation time, 450 nm blue laser light emission time, 980 nm red laser light emission time, postoperative bladder irrigation time, international prostate symptom score (IPSS), quality of life score (QoL), maximum flow rate (Qmax), post-void residual (PVR), international index of erectile function-5 (IIEF-5), ejaculation and incidence of postoperative complications were analyzed. [Results] All operations were successful, without conversion to open or transurethral resection of the prostate (TURP). The operation time was 12.7 (10.8, 14.3) min, the 450 nm blue laser light emission time was 11.7 (9.6, 13.3) min, the 980 nm red laser light emission time was 1.0 (1.0, 2.0) min, the postoperative bladder irrigation time was 5.0 (2.8, 8.0) h, the total hospital stay was 6.0 (4.0, 7.0) d, the postoperative hospital stay was 2.0 (2.0, 3.0) d, and the postoperative catheter retention time was 2.0 (0, 2.0) d. After 3 or 6 months of follow-up, the IPSS, QoL and PVR were significantly lower than those before operation, while the Qmax was significantly higher, with significant differences (P<0.001); but there was no significant difference in the IIEF-5 score (P>0.05). During the 3-month follow-up, 4 patients (11.8%) had fever; during the 3-6 month follow-up, 1 patient (2.9%) had external urethral stricture; of the 8 patients with sexual life before operation, 1 (12.5%) had retrograde ejaculation after operation.No hematuria occurred. [Conclusion] BLTUIP is a new, safe and efficient surgical treatment for BPH with a volume ≤30 mL, which can shorten the operation time, reduce postoperative complications, and improve the quality of life.

[Objective] To explore the number of examined lymph nodes (ELN) and positive lymph node ratio (LNR) in the prediction of 5-year and 10-year overall survival (OS) and cancer-specific survival (CSS) of prostate cancer (PCa) patients, so as to provide reference for clinical practice. [Methods] Information of PCa patients screened in the Surveillance, Epidemiology and End Results (SEER) database during 2010-2020 were analyzed. A total of 1842 PCa patients were assigned to the training set (n=1290) and validation set (n=552) in a 7∶3 ratio with R 4.3.0 software. Significant factors in the multivariate Cox proportional risk regression model were adjusted, restricted cubic spline plots (RCS) were plotted, the optimal cut-off values of ELN and LNR were determined, and the 5-year and 10-year OS and CSS were analyzed with restricted mean survival time (RMST). [Results] Multivariate Cox analysis showed that there was a 2.9% reduction in the risk of death with an increase of 1-unit ELN and a 3.1% reduction in the risk of cancer-specific death. There was a 481.4% increase in the risk of death with a 1-unit increase in LNR and a 667.5% increase in the risk of cancer-specific death. The risk of overall death and cancer-specific death in ELN and PCa patients showing a non-linear relationship (P<0.001), while in the LNR and PCa patients showing a linear relationship (P>0.05). RMST results showed that the optimal ELN range for evaluating OS was 12-29, the optimal ELN range for assessing CSS was 12-25, LNR>0.152 indicated poor prognosis. [Conclusion] We have clarified the range of ELN and LNR, which can provide reference for the clinical precision diagnosis and treatment of PCa.

Objective:To explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome (BOFS) and summarize the prenatal phenotype of BOFS patients.Methods:A pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject. Clinical data of the pedigree was collected. The fetus was subjected to routine prenatal ultrasound scan. Trio-whole exome sequencing (trio-WES) was carried out for the fetus and its parents, and candidate variant was verified by Sanger sequencing. Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Ultrasound exam suggested the fetus had cleft lip and palate. Its father had presented with high palatal arch, prematurely grayed hair, occult cleft lip, congenital preauricular fistula, red-green color blindness and unilateral renal agenesis. Its grandfather also had high palatal arch, prematurely gray hair, protruding ears, congenital preauricular fistula and hearing disorders. Trio-WES revealed that the fetus and its father had both harbored a heterozygous c. 890-1G>A variant of the TFAP2A gene. The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+ PM2_Supporting). Combined with 36 similar cases retrieved from the literature, the prenatal phenotypes of BOFS patients had included growth restriction (25/37), renal abnormalities (10/37), cleft lip and palate (5/37) and oligohydramnios (5/37). Conclusion:The c. 890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree. Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene. The common prenatal phenotypes of BOFS have included growth restriction, renal abnormalities, cleft lip and palate and oligohydramnios. Delineation of the intrauterine phenotype of BOFS may facilitate its prenatal diagnosis, clinical diagnosis, treatment and genetic counseling.

The safety and survival benefits of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer have been confirmed by randomized controlled trials and clinical studies abroad. However, real-world studies remain lacking. In this article, we review the progress of real-world studies of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer and the problems faced in clinical practice against the background of differentiated real-world studies. Further research is needed to address clinically important issues, such as individualized dosing, combination dosing, and monitoring of adverse effects.

Skin injuries always disturb people's normal life, even seriously damage the body health. Thus, it is very necessary to use medical dressings to protect and treat skin wounds. Compared with traditional dressings, novel biological dressings develop more rapidly and their application scope is gradually expanding. Collagen is a natural biological material that can promote wound healing and it also has unique functional advantages in care and treatment. At present, collagen-based medical dressings has become one of the preferred choices to assist wound healing. The authors summarize the source, functional advantages and product classification of collagen-based dressings, and introduce the characteristics and applications of various collagen-based dressings, to provides a reference for further research of the collagen-based wound dressings.

Objective:To identify the pathogenic gene of a pedigree with symphalangism and to prove the pathogenicity of this locus in vitro.Methods:The clinical data of patients’families were collected at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, peripheral blood was collected and genomic DNA was extracted and NOG, FGF9, GDF5 exon regions were amplified by PCR, and the exon gene mutations were detected by first-generation sequencing technique. The structure of noggin-GDF5 protein complex was simulated in silicon. COS-7 cells were transfected with 5 μg empty plasmid, wild type plasmid and V202G mutant plasmid in vitro. Each group of plasmids was transfected into 3 well cells. The experiment was repeated for 3 times, and the expression of noggin protein was detected by Western blotting. C2C12 cells were also transfected with the above plasmids in vitro for osteogenic differentiation. By applying alkaline phosphatase staining and quantitative assay. Relative expression level of osteoblast-related genes Col1α1, ALP and Runx2 were detected by qRT-PCR. Each group of plasmids was transfected into 3 well cells, and the experiment was repeated for 3 times. All statistical analysis were performed by Prism 6 software. The result were shown as mean±standard deviation, and the comparison between groups was done by unpaired t-test. Data were considered statistically significant when P value is less than 0.05. Results:Both the proband and his mother suffered from symphalangism. The result of Sanger sequencing showed that there was a heterozygous missense mutation of NOG gene (p.V202G) in all patients in this pedigree. No disease-related mutations were detected in FGF9 and GDF5. Computer three-dimensional mechanism simulation showed that the site was located at the α helix. The result of Western blotting showed that the expression of mutant protein was significantly lower than that of wild type. Osteogenic differentiation in vitro showed that the inhibitory effect of V202G mutant protein on osteogenic differentiation decreased. The quantitative result of alkaline phosphatase staining showed that the alkaline phosphatase activity in the vector group was (12.3±0.8) U/L, and the alkaline phosphatase activity in the wild type plasmid group was (2.6±0.3) U/L, which was significantly lower than that in the vector group ( t=11.550, P<0.001). The alkaline phosphatase activity in the mutant plasmid group was (10.8±0.3) U/L. There was no significant difference between the mutant group and the vector group ( t=1.830, P=0.141). The mRNA expression level of osteogenesis-related genes was consistent with the above result . Compared with vector group, the expression of osteogenesis-related genes in wild-type noggin group decreased significantly ALP、 Col1α1 and Runx2 ( t=5.987, 4.498, 4.170; P=0.004, 0.011, 0.014). There was no significant difference between mutant plasmid group and blank vector group in ALP、 Col1α1 and Runx2 ( t=0.433, 0.177, 1.159; P=0.688, 0.868, 0.311). Conclusions:NOG gene c. 605T < G p. V202G is a novel mutation in symphalangism, which is located in the α helix of noggin protein, leading to the decrease of the expression of noggin protein and the manifestation of ankylosis.

Objective:To identify the pathogenic gene of a pedigree with symphalangism and to prove the pathogenicity of this locus in vitro.Methods:The clinical data of patients’families were collected at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, peripheral blood was collected and genomic DNA was extracted and NOG, FGF9, GDF5 exon regions were amplified by PCR, and the exon gene mutations were detected by first-generation sequencing technique. The structure of noggin-GDF5 protein complex was simulated in silicon. COS-7 cells were transfected with 5 μg empty plasmid, wild type plasmid and V202G mutant plasmid in vitro. Each group of plasmids was transfected into 3 well cells. The experiment was repeated for 3 times, and the expression of noggin protein was detected by Western blotting. C2C12 cells were also transfected with the above plasmids in vitro for osteogenic differentiation. By applying alkaline phosphatase staining and quantitative assay. Relative expression level of osteoblast-related genes Col1α1, ALP and Runx2 were detected by qRT-PCR. Each group of plasmids was transfected into 3 well cells, and the experiment was repeated for 3 times. All statistical analysis were performed by Prism 6 software. The result were shown as mean±standard deviation, and the comparison between groups was done by unpaired t-test. Data were considered statistically significant when P value is less than 0.05. Results:Both the proband and his mother suffered from symphalangism. The result of Sanger sequencing showed that there was a heterozygous missense mutation of NOG gene (p.V202G) in all patients in this pedigree. No disease-related mutations were detected in FGF9 and GDF5. Computer three-dimensional mechanism simulation showed that the site was located at the α helix. The result of Western blotting showed that the expression of mutant protein was significantly lower than that of wild type. Osteogenic differentiation in vitro showed that the inhibitory effect of V202G mutant protein on osteogenic differentiation decreased. The quantitative result of alkaline phosphatase staining showed that the alkaline phosphatase activity in the vector group was (12.3±0.8) U/L, and the alkaline phosphatase activity in the wild type plasmid group was (2.6±0.3) U/L, which was significantly lower than that in the vector group ( t=11.550, P<0.001). The alkaline phosphatase activity in the mutant plasmid group was (10.8±0.3) U/L. There was no significant difference between the mutant group and the vector group ( t=1.830, P=0.141). The mRNA expression level of osteogenesis-related genes was consistent with the above result . Compared with vector group, the expression of osteogenesis-related genes in wild-type noggin group decreased significantly ALP、 Col1α1 and Runx2 ( t=5.987, 4.498, 4.170; P=0.004, 0.011, 0.014). There was no significant difference between mutant plasmid group and blank vector group in ALP、 Col1α1 and Runx2 ( t=0.433, 0.177, 1.159; P=0.688, 0.868, 0.311). Conclusions:NOG gene c. 605T < G p. V202G is a novel mutation in symphalangism, which is located in the α helix of noggin protein, leading to the decrease of the expression of noggin protein and the manifestation of ankylosis.