Conditional survival nomogram for patients with colon mucinous adenocarcinoma to predict prognosis: a dynamic survival analysis.

The aim was to assess conditional survival for colon mucinous adenocarcinoma (MAC) patients, and to construct nomograms to predict conditional survival probability. Survival analysis was done using conditional survival, which was defined as the probability of surviving additional y years for patients who have survived for x years. The mathematical definition was express as: CS (y|x) = S (x + y)/S (x). Cox regression analyses were used to identify prognostic factors. A nomogram is constructed to predict conditional disease-free survival (DFS) and overall survival (OS) probability according to years that already survive. A total of 179 colon MAC patients were included. The 5-year DFS was 67% after surgery, and the 5-year survival probability of patients, who already survived 1, 2, 3, and 4 years were 75%, 87%, 95%, and 98%, respectively. The 5-year OS was 73% after surgery and increased to 76%, 82%, 88%, and 92% at 1, 2, 3, and 4 years, respectively. Subgroup analyses demonstrated the superiority of conditional survival was more pronounced in advanced stages than in stage I. And pT stage, pN stage, and lymphovascular invasion were significantly associated with DFS and OS. Conditional survival nomograms were constructed to predict the 5-year conditional DFS and OS probability given survival for 1, 2, 3, 4 years after surgery. Conditional survival can provide dynamic survival probability according to years that already survive, especially for patients with advanced stages. Taking into account the years already survived accounted for, novel nomograms contributed to effectively predicting conditional survival.

Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.

Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

Comprehensive genomic profiling of breast cancers characterizes germline-somatic mutation interactions mediating therapeutic vulnerabilities.

Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.

Application of the cell-based RT-qPCR assay (C-QPA) for potency detection of the novel trivalent rotavirus vaccine in China.

BACKGROUND: Because of the deficiencies of traditional methods in multivalent rotavirus vaccine potency detection, a cell-based quantitative RT-qPCR assay (C-QPA) was established and validated for specificity, precision, and accuracy. METHODS: In order to further validate the robustness of this method in actual titer detection, the linear range and the practical application under different conditions were tested using monovalent and trivalent rotavirus samples and standards. RESULTS: Results showed that the linear range was 2.0-6.5, 3.9-8.3, and 3.5-8.1 UI (unit of infectivity) for G2, G3, and G4, respectively. Besides, unknown sample with high titer exceeding the linear range can be calculated by dilution. The UIs of serotypes G2, G3, and G4 in monovalent and trivalent rotavirus samples showed a relative deviation ≤4.10%, and the monovalent samples of the same serotype with or without protective agents showed a relative deviation ≤4.28%; the coefficient of variation (CV) of at least 176 tests (548 individual runs) of 3 in vitro-transcribed RNA standards with certain concentrations was not higher than 6.50%; the results of the trivalent samples tested by more than 149 times in 5 years (467 individual runs) showed the CVs lower than 12.66%; 15 samples detected by one laboratory showed a CV lower than 9.83%, while other three samples tested by two independent laboratories showed a CV lower than 6.90%. CONCLUSION: In summary, the C-QPA has good linearity, durability, repeatability, and reproducibility in practical application and has been proved by the authority to be widely used in the production, quality control and release of the recently licensed trivalent vaccine in China.

Double J stent combined with pyelostomy tube in pediatric laparoscopic pyeloplasty: a 5-year clinical experience in a single center.

OBJECTIVE: To compare the outcome of using a double J (DJ) stent combined with pyelostomy tube with a DJ stent alone in laparoscopic pyeloplasty (LP) for pediatric ureteropelvic junction obstruction (UPJO). METHODS: A retrospective review of all patients with UPJO treated with LP between January 2017 and November 2021 was conducted in our center. According to different postoperative drainage methods patients were divided into a DJ stent group (52 cases) and a DJ stent combined with pyelostomy tube group (combination group, 41 cases). Operative time, bleeding volume, perirenal drainage stent removal time, postoperative hospital stay, postoperative complications, and renal function recovery were compared between the two groups. Renal ultrasound and diuretic renogram (DR) were used for preoperative and postoperative follow-up. RESULTS: A total of 52 patients were in the DJ stent group and 41 patients in the combination group. The mean hospital stay was 6.46 ± 2.66 days in the DJ stent group and 5.22 ± 1.63 days in the combination group (p < 0.05). Postoperative complications developed in 14 out of 52 patients in the DJ stent group (26.9%), while complications developed in 8 out of 41 patients in the combination group (19.5%) (p > 0.05). Non-catheter-related complications developed in 10/52 patients in the DJ stent group (19.2%) and only 1/41 patients in the combination group (2.4%) (p < 0.05). The renal function and renal cortex thickness in both groups were improved. CONCLUSION: Both the DJ stent drainage and the DJ stent combined with pyelostomy drainage are safe and effective. We should fully consider the patient's preoperative and intraoperative conditions and choose appropriate drainage methods. A DJ stent combined with pyelostomy tube can reduce non-catheter related complications, facilitate postoperative recovery, and the hospital stay was significantly shorter than the DJ stent group. However, it is necessary to pay attention to the nursing treatment of the pyelostomy tube and guard against the occurrence of pyelostomy tube shedding.

Preparation and Performance Study of Microemulsion Acid for Comprehensive Plugging Removal in Carbonate Reservoir.

Matrix acidification is one of the most effective stimulations to dissolve scales and remove damage in carbonate reservoirs. However, existing acid systems are difficult to dissolve organic and inorganic scales simultaneously, and complex multi-stage alternative injection often introduces new precipitation and damages the reservoir. Here, based on the retardation ability of emulsified acid and the stable structure of microemulsion, an oil-phase solvent was preferably selected, and the surfactant and cosurfactant were optimized to prepare an acid-in-oil type microemulsion acid capable of dissolving both organic and inorganic scales and high solubilizing for hydrochloric acid. Based on the rotating disc experiment, scale dissolution experiment and acid driving experiment, the acid-rock reaction kinetics, scale dissolution ability and acidizing and plugging removal performance of microemulsion acid in a carbonate reservoir were systematically studied and compared. The results show that Solvesso 150 (aromatic solvent) has the advantages of low toxicity, high flash point and high-scale dissolving ability. At NP-4: OP-10: A (cosurfactant) = 3:3:4, the microemulsion acid system has the strongest ability to solubilize hydrochloric acid and can solve the problem of low H+ concentration. The particle size of microemulsion acid is smaller compared to emulsified acid. At 60 °C, the mass transfer coefficient of microemulsion acid is 3.2 × 10-8 cm2/s, which is one order of magnitude less than that of emulsified acid. Microemulsion acid shows good solubility performance in dissolving organic and inorganic scales, and the comprehensive solubility of mixed scales can reach 98.28%. The stronger scale solubilization ability and lower acid-rock reaction rate enable microemulsion acid to form a thin and straight main wormhole, thus enhancing the acidizing and plugging removal effect. This study can solve the problem of poor hydrochloric acid solubilization ability of microemulsion acid to a certain extent, which provides theoretical and data support for the research and development of microemulsion acid and the efficient plugging removal technology for carbonate reservoirs.

Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis.

BACKGROUND & AIMS: Tumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet the indications for genomics-guided precision medicine and immunotherapy must be better understood and defined. METHODS: We prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel and evaluated the clinical significance of single-gene somatic mutations and co-occurring events in metastatic CRC, as well as their functional effects and tumorigenic mechanisms. We systematically assessed the heterogeneity of the tumor immune microenvironment in different genomic contexts through the combined analysis of Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, and single-cell sequencing. RESULTS: Single-gene somatic mutations in BRAF or RBM10 were associated with shorter progression-free survival in patients with metastatic CRC. Functional studies suggested RBM10 acts as a tumor suppressor in CRC development. Co-mutations of KRAS/AMER1 or KRAS/APC were enriched in the metastatic cohort, which had poor progression-free survival and did not benefit from bevacizumab due to accelerated drug metabolism. Forty patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 37.5% of these tumors had secondary-hit events with loss of heterozygosity or biallelic alterations. A high tumor insertion or deletion burden with high microsatellite instability suggested immunogenicity with numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation with ultrahigh tumor mutation burden indicated a relatively quiescent immunophenotype. The heterogeneous genomic-immunologic interactions were reflected in the divergent neoantigen presentation and depletion, immune checkpoint expression, PD-1/PD-L1 interaction, and T-cell responsiveness to pembrolizumab. CONCLUSIONS: Our integrated analysis provides insights into CRC prognostic stratification, drug response, and personalized genomics-guided targeted and immunotherapies.

An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression.

Dysregulation of RNA-binding proteins (RBP) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in patients with TNBC. SNRPC ablation significantly impaired the proliferation, migration, and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2, and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1-ß-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC. SIGNIFICANCE: A functional CRISPR screen identifies SNRPC as an RNA-binding protein that promotes the aggressiveness of breast cancer by facilitating Pol II-controlled transcription of oncogenes.

Effect of pneumovesicoscopic cohen surgery with adjustable suspension technique through the urethra on the treatment of primary vesicoureteral reflux disease in infants.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra for the treatment of primary vesicoureteral reflux disease in infants. METHODS: This study retrospectively analysed the clinical data of 31 infants who underwent pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra in our hospital from January 2019 to December 2020. We also collected the clinical data of 29 infants who underwent open Cohen surgery in our hospital from January 2015 to December 2018 as a control variable. The clinical efficacy of the two groups was compared. RESULT: All pneumovesicoscopic Cohen surgeries were successfully completed and no patients were converted to open surgery. The amount of bleeding, duration of postoperative analgesia, duration of postoperative haematuria, incision size and length of hospital stay in the pneumovesicoscopic surgery group were significantly lower than those in the open surgery group (P < 0.05). The operation time of the pneumovesicoscopic surgery group was significantly longer than that of the open surgery group (P < 0.05). Both groups were followed for six months after surgery. At the 6-month follow-up time, there were no significant differences in the degree of hydronephrosis, renal scarring, renal atrophy, glomerular filtration rate, or KIM-1 and MCP-1 expression between the two groups (P > 0.05). CONCLUSION: Pneumovesicoscopic Cohen surgery with an adjustable suspension technique through the urethra for the treatment of primary vesicoureteral reflux disease in infants was safe and effective. This procedure had the advantages of less trauma, quick recovery and good cosmetic effects.

PAnno: A pharmacogenomics annotation tool for clinical genomic testing.

Introduction: Next-generation sequencing (NGS) technologies have been widely used in clinical genomic testing for drug response phenotypes. However, the inherent limitations of short reads make accurate inference of diplotypes still challenging, which may reduce the effectiveness of genotype-guided drug therapy. Methods: An automated Pharmacogenomics Annotation tool (PAnno) was implemented, which reports prescribing recommendations and phenotypes by parsing the germline variant call format (VCF) file from NGS and the population to which the individual belongs. Results: A ranking model dedicated to inferring diplotypes, developed based on the allele (haplotype) definition and population allele frequency, was introduced in PAnno. The predictive performance was validated in comparison with four similar tools using the consensus diplotype data of the Genetic Testing Reference Materials Coordination Program (GeT-RM) as ground truth. An annotation method was proposed to summarize prescribing recommendations and classify drugs into avoid use, use with caution, and routine use, following the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC), etc. It further predicts phenotypes of specific drugs in terms of toxicity, dosage, efficacy, and metabolism by integrating the high-confidence clinical annotations in the Pharmacogenomics Knowledgebase (PharmGKB). PAnno is available at https://github.com/PreMedKB/PAnno. Discussion: PAnno provides an end-to-end clinical pharmacogenomics decision support solution by resolving, annotating, and reporting germline variants.

Laparoscopic-assisted Soave procedure for Hirschsprung disease: 10-year experience with 106 cases.

BACKGROUND: The purpose of this study was to summarize the clinical experience and 10 year follow-up results of laparoscopic assisted Soave procedure for the treatment of long-segment Hirschsprung disease (HD). METHODS: From January 2010 to February 2020, 106 children with long-segment HD participated in this study. The laparoscopic-assisted Soave procedure was performed for the treatment of long-segment HD. The follow-up time was two weeks, one month, and three months after the operation, and then every six months to one year. RESULTS: The operation was successful for all 106 children. All patients were discharged 5-7 days after the operation. The median time in surgery was 150 (100-190) minutes, and the median volume of bleeding was 6 (3-10) ml. The short-term postoperative daily defecation frequency was 4-11 times, 3-7 times within 6 months, and 2-3 times after 6-12 months. Postoperative complications included anastomotic leakage in two cases, perianal dermatitis in 13 cases, anastomotic stenosis in four cases, adhesive bowel obstruction in two cases, enterocolitis in 16 cases, soiling in 11 cases, and constipation recurrence in three cases. CONCLUSIONS: The laparoscopic-assisted Soave procedure is a safe and effective surgical method for treating long-segment HD, and it causes little trauma or bleeding and has a fast postoperative recovery. Yet some complications may occur. Preoperative diagnosis, intraoperative and postoperative standardized processing can reduce the postoperative complications.

Single-site laparoscopic high ligation of the extraperitoneal hernia sac with an epidural needle for incarcerated ovarian hernia in infants.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of single-site laparoscopic extraperitoneal hernia sac ligation with an epidural needle for incarcerated ovarian hernias in infants and young children. METHODS: The clinical data of 38 infants with incarcerated ovarian hernias who underwent single-site laparoscopic extradural needle extraperitoneal hernia sac ligation from January 2015 to January 2018 were retrospectively analysed. RESULTS: All procedures were successfully performed using laparoscopy with no need for conversion to open surgery. The time of hospital stay was 1.30 ± 0.39 days. During hospitalization and follow-up, there were no complications, such as intestinal or bladder injury, abdominal wall vascular injury, ovarian atrophy, hernia recurrence or contralateral indirect hernia. However, three patients experienced complications, including two cases of poor healing of the umbilical incision and one case of suture granuloma. CONCLUSIONS: Single-site laparoscopic high ligation of the extraperitoneal hernia sac with an epidural needle is a safe and feasible method for the treatment of incarcerated ovarian hernias in infants and young children. It has the advantages of minimal trauma, no scarring and good cosmetic effects.

Single-port laparoscopic percutaneous closure of the internal ring for scarless repair of inguinal hernias in girls.

PURPOSE: The purpose of this study was to summarize the clinical experience with laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle for inguinal hernias in girls. MATERIAL AND METHODS: A total of 462 girls with inguinal hernias participated in this study from January 2013 to June 2019. Laparoscopic percutaneous extraperitoneal closure of the internal ring via an epidural needle was used to treat these patients. RESULTS: All 462 girls with an inguinal hernia successfully underwent laparoscopic surgery. The operative times for unilateral and bilateral inguinal hernias were 15 (11-25) minutes and 23 (18-33) minutes, respectively. All patients were discharged 1-2 days after the operations. During the hospitalization and follow-up periods, none of the following complications were observed: hernia recurrence, umbilical hernia, abdominal wall vascular injury, intestinal injury or bladder injury. However, there were six patients with complications: two cases of poor healing of the umbilical incision, three cases of suture granulomas and one case of groin traction pain and discomfort. CONCLUSION: Laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle is a safe and feasible method for the treatment of inguinal hernias in girls. This method has the advantages of limited trauma, no scarring and a good cosmetic effect.

Clinical Efficacy of an Indwelling Transanal Tube for the Prevention of Anastomotic Leakage After Hirschsprung's Disease: A Single Center Experience with Chinese Patients.

Background: The aim of this study was to investigate the clinical effectiveness of an indwelling transanal tube for the prevention of anastomotic leakage (AL) after a radical operation for Hirschsprung's disease (HD). Methods: We retrospectively analyzed the clinical data from 158 patients who had undergone laparoscopic-assisted Soave procedures for HD at our hospital from May 2015 to May 2019. Patients were divided into two groups depending upon whether the anal drainage tube was retained or not retained: an indwelling group (group A, n = 86) and a no-indwelling group (group B, n = 72). Results: All 158 children had a successful operation by a laparoscopic technique. There was no significant difference in the duration of the operation, the length of the incision, the amount of bleeding, or the postoperative hospitalization time between the two groups. Compared with the no-indwelling group, maintaining the transanal tube had significant advantages for preventing incidences of AL (P < .05). The 4-year follow-up showed that the incidence of postoperative enterocolitis with the indwelling transanal tube was significantly lower than in the group without the drainage tube (P < .05). Conclusions: The laparoscopic-assisted Soave procedure with an indwelling transanal tube is a safe and feasible method for the treatment of HD in children. This method can not only drain intestinal contents but also reduce the occurrence of AL.

Using Elevated Cholesterol Synthesis as a Prognostic Marker in Wilms' Tumor: A Bioinformatic Analysis.

BACKGROUND: Wilms tumor is the most common renal malignancy of children. Identifying factors that could predict the prognosis of patients with Wilms tumor is clinically meaningful. Many studies found tumors with elevated cholesterol synthesis that are featured with dismal prognosis. Even in some clinical trials, people with excessive dietary cholesterol intake and high plasma low-density lipoprotein levels are observed to have increased risk for cancer. However, the role of cholesterol biosynthesis in Wilms tumor has not yet been well clarified. METHODS: RNA sequencing transcriptome data and all corresponding clinicopathological information used in our study were downloaded from the TARGET database. High-throughput sequencing (Fragments Per Kilobase of transcript per Million fragments mapped) data sets of 130 tumor samples and 6 normal samples were obtained for further analysis. RESULTS: Wilms tumor samples with higher activity of cholesterol synthesis are characterized with worse overall survival (P < 0.05). In addition, Wilms tumor samples with mitigated activity of cholesterol synthesis are featured with better dendritic cell (DC) function and cytolytic activity (P < 0.05). Furthermore, we constructed a prognosis model based on differential expressed cholesterol synthesis-related genes (DECSG), which could predict the OS of patients with Wilms tumor accurately. KEGG and GO analysis of differential expressed genes between tumor samples with high and low cholesterol synthesis indicated that DECSGs are highly enriched in "mitosis nuclear division," "nuclear division," "chromosome segregation," "cell cycle," "Spliceosome," and "RNA transport." CONCLUSIONS: In conclusion, our study reported increased cholesterol synthesis in Wilms tumor predicts a worse prognosis and mitigated cytolytic activity, DC function, and MHC I signature in the tumor microenvironment. We also constructed a prognosis model for predicting the OS of patients with good accuracy, which is promising in clinical translation. Future studies should focus on the detailed mechanism that caused increasing cholesterol which promotes tumor progression and undermines patients' survival.

Clinical effect of minimally invasive surgery for inguinal cryptorchidism.

BACKGROUND: The purpose of this study was to investigate the clinical effect of minimally invasive surgery for inguinal cryptorchidism. METHODS: The patients were divided into the minimally invasive surgery group (n = 100) and the traditional surgery group (n = 58). In the minimally invasive surgery group, patients with low inguinal cryptorchidism (n = 54) underwent surgery with a transscrotal incision, and patients with high inguinal cryptorchidism (n = 46) underwent laparoscopic surgery. RESULTS: There was no difference in the hospital stay duration or cost between the minimally invasive surgery group and the traditional surgery group (P > 0.05). As for the operative time, minimally invasive surgery of low inguinal cryptorchidism was shorter than traditional surgery (P = 0.033), while minimally invasive surgery of high inguinal cryptorchidism was comparable to traditional surgery (P = 0.658). Additionally, there were no cases of testicular atrophy, testicular retraction, inguinal hernia or hydrocele in either group. There was no significant difference in the incidence of poor wound healing between the two groups (P > 0.05). Although there was no significant difference in the incidence of scrotal hematoma between the two groups (P > 0.05), the incidence in the minimally invasive surgery group was higher than that in the traditional surgery group. CONCLUSIONS: Minimally invasive surgery including a transscrotal incision for low inguinal cryptorchidism and laparoscopic surgery for high inguinal cryptorchidism is as safe and effective as traditional surgery, and could also provide a good cosmetic effect for children.

Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Clinical efficacy of transverse preputial island flap urethroplasty for single-stage correction of proximal hypospadias: a single-centre experience in Chinese patients.

BACKGROUND: This study was designed to summarize the clinical outcomes of transverse preputial island flap urethroplasty for single-stage correction of proximal hypospadias in our hospital. METHOD: This study retrospectively analysed the clinical data, including the preoperative general information, intraoperative and postoperative data, and follow-up data, of 155 children with proximal hypospadias who were admitted to our hospital from January 2009 to January 2019. RESULTS: During follow-up, a total of 92 postoperative complications occurred, and 41 patients underwent reoperation. There were 49 patients with urinary fistula, 26 patients with urethral stricture, 9 patients with urethral diverticulum and 8 patients with urinary tract infection. Regarding the family members' satisfaction with the cosmetic appearance of the penis, the satisfaction rate with the urinary meatus was 85.2%, the satisfaction rate with the glans appearance was 87.7%, the satisfaction rate with the the appearance of the foreskin of the penis was 92.3%, and the satisfaction rate with the overall penis shape was 89.0%. CONCLUSION: Proximal hypospadias is a serious condition that is often combined with severe chordee, and transverse preputial island flap urethroplasty for single-stage correction is an effective surgical procedure for treating this condition.

Establishment of a cell-based quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay for detection of multivalent rotavirus vaccine.

Because of deficiencies of traditional potency tests in rotavirus detection, a one-step TaqMan probe-based quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay combined with cell-based method was established to determine the infectious potency of the target virus in multivalent live rotavirus vaccines in vitro. Series dilutions of rotavirus samples were inoculated into Vero cells and cultured for 24 hours. The cells were lysed and the potency was detected by RT-qPCR. The reference standards with a known titer (lgCCID50 /mL) were assayed in parallel, and the potencies of each sample were determined using parallel line method. The specificity, precision and accuracy of the assay were evaluated, respectively. The results showed that messenger RNA produced during rotavirus replication was the primary template of RT-qPCR and the primers and probes were specific to each strain. The coefficient of variation of different wells and different working days did not exceed 6% and the results of the assay were proved to be concordant with those of cell culture infective dose 50% with a relative deviation less than 5%. This assay is a more rapid, cost-effective and high-throughput way for detecting multivalent rotavirus vaccine, and will be a valuable tool in the quality control and stability monitoring of live multivalent rotavirus vaccine.