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.

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.

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.

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.

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.

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.

PreMedKB: an integrated precision medicine knowledgebase for interpreting relationships between diseases, genes, variants and drugs.

One important aspect of precision medicine aims to deliver the right medicine to the right patient at the right dose at the right time based on the unique 'omics' features of each individual patient, thus maximizing drug efficacy and minimizing adverse drug reactions. However, fragmentation and heterogeneity of available data makes it challenging to readily obtain first-hand information regarding some particular diseases, drugs, genes and variants of interest. Therefore, we developed the Precision Medicine Knowledgebase (PreMedKB) by seamlessly integrating the four fundamental components of precision medicine: diseases, genes, variants and drugs. PreMedKB allows for search of comprehensive information within each of the four components, the relationships between any two or more components, and importantly, the interpretation of the clinical meanings of a patient's genetic variants. PreMedKB is an efficient and user-friendly tool to assist researchers, clinicians or patients in interpreting a patient's genetic profile in terms of discovering potential pathogenic variants, recommending therapeutic regimens, designing panels for genetic testing kits, and matching patients for clinical trials. PreMedKB is freely accessible and available at http://www.fudan-pgx.org/premedkb/index.html#/home.

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.

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.

The Safety and Effectiveness of Laparoscopic versus Open Surgery for Congenital Hypertrophic Pyloric Stenosis in Infants.

BACKGROUND This study aimed to investigate the safety and effectiveness of laparoscopic pyloromyotomy for infants with congenital hypertrophic pyloric stenosis. MATERIAL AND METHODS The clinical data of 233 infants with congenital hypertrophic pyloric stenosis who were treated at our hospital from January 2013 to January 2018 were analyzed retrospectively. The patients were divided into 2 groups: the laparoscopic group (group A, n=126) and the conventional operation group (group B, n=107). RESULTS Laparoscopic surgery was successfully performed in all patients in the laparoscopic group, and none of the surgeries were converted to open surgery. Compared with traditional surgery, laparoscopic surgery has obvious advantages in operation time (29.8±12.9 minutes versus 37.2±17.5 minutes, P=0.012), postoperative feeding time (10.3±2.2 hours versus 15.2±4.1 hours, P=0.035), postoperative hospitalization time (2.8±0.7 days versus 3.5±1.9 days, P=0.013), incision length (0.9±0.2 cm versus 3.3±0.8 cm, P=0.002) and poor wound healing (0 versus 6, P=0.007). No complications, such as bleeding, gastric perforation, duodenal injury, abdominal infection or recurrent vomiting, were observed in the 2 groups. The growth and development (weight and height) of the infants in both groups were normal. CONCLUSIONS Laparoscopic pyloromyotomy has the same safety and effectiveness as the traditional operation and has the advantages of less trauma, faster recovery and cosmetically pleasing incisions.

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.

Transscrotal transverse incision for the treatment of middle and low cryptorchidism in children: experience from 796 cases.

BACKGROUND: The purpose of this study was to summarize our clinical experience with transscrotal transverse incision in the treatment of low and middle cryptorchidism in children. METHODS: A total of 796 children with low or middle cryptorchidism participated in this study from March 2012 to May 2018. Transscrotal transverse incision was used to treat low and middle cryptorchidism. Symptoms and signs were followed up at 1 week, 1 month, 3months and every six to 12 months thereafter. RESULTS: Testicular descent fixation through transverse scrotal incision was successfully performed in all 796 children. All patients were discharged 1-2 days after the operation. During hospitalization and follow-up, 35 patients had complications, including 7 cases of cryptorchidism recurrence, 5 cases of poor scrotal incision healing, and 23 cases of scrotal haematoma. There were no complications, such as bladder injury, testicular atrophy, inguinal hernia or hydrocele. CONCLUSION: Transscrotal transverse incision is a safe and feasible method for the treatment of middle and low cryptorchidism. It has the advantages of less trauma and an aesthetic scar after operation.

Metabolomics as a potential method for predicting thyroid malignancy in children and adolescents.

PURPOSE: To identify potential metabolic biomarkers for distinguishing malignant and benign thyroid nodules in children and adolescents using a metabolomics approach. METHODS: A total of 96 consecutive patients (median age 14.29 ± 2.31 years, range 9-18 years) who underwent thyroidectomy and 40 healthy controls were enrolled. Patients were assigned to the papillary thyroid carcinoma and benign thyroid adenoma groups according to postoperative pathologic biopsy. Plasma samples were preoperatively collected, and multivariate analysis was performed to identify differential metabolites. RESULTS: Papillary thyroid carcinoma could be distinguished not only from healthy serum but also from benign thyroid adenoma according to the metabolic profiles. A total of 17 metabolites were identified. Compared with those from benign thyroid adenoma patients and healthy controls, the metabolites from papillary thyroid carcinoma patients, including leucine, lactate, alanine, glycine, acetate, lysine and choline, were increased, while glucose was decreased. CONCLUSION: The metabolomics method based on proton nuclear magnetic resonance has great potential for identifying papillary thyroid carcinoma in children and adolescents. Lactate and glycine may be used as potential serum markers for the diagnosis of papillary thyroid carcinoma.

Valuation effect of capital account liberalization: Evidence from the Chinese stock market.

This paper examines the valuation effect of capital account liberalization. Using an event study approach and the policy announcement for RMB Qualified Foreign Institutional Investors (short for RQFII) as the event date, we find that overall, the stock market responded positively to the capital account liberalization announcement. In addition, we provide some heterogeneity that firms with more stringent financing constraints earn higher returns than their counterparts. Finally, existing local institutions play an important role in determining announcement returns.

Laparoscopic Disconnected Pyeloplasty to Treat Ureteropelvic Junction Obstruction (UPJO) in Children.

BACKGROUND The aim of this study was to assess the safety and clinical effectiveness of laparoscopic disconnected pyeloplasty in treating ureteropelvic junction obstruction (UPJO) in children. MATERIAL AND METHODS We retrospectively analyzed the clinical data of 122 young children with UPJO treated from February 2015 to February 2018 at our hospital. According to the surgery type, the patients were divided into 2 groups: a laparoscopic surgery group (group A, n=69) and a traditional open surgery group (group B, n=53). RESULTS The success rate of laparoscopic disconnected pyeloplasty was 100%, and none of the patients were converted to open surgery. The mean duration of use of painkillers was 27.6±11.3 h in group A and 58.2±18.2 h in group B (p=0.012), the postoperative hospital stay was 7.8±1.5 days in group A and 11.5±2.6 days in group B (p=0.041), and the length of the incision was 1.5±0.4 cm in group A and 5.2±1.1 cm in group B (p=0.007). The incidence rate of poor surgical wound healing was 0% in group A and 7.5% in group B (p=0.020). The incidence rate of ureteral stricture was 4.3% in group A and 3.8% in group B (p=0.874) during follow-up. The 1-year follow-up showed that both the anterior and posterior diameters and glomerular filtration rate were significantly improved from the preoperation period. CONCLUSIONS Laparoscopic disconnected pyeloplasty to treat UPJO in young children has the same early clinical effectiveness and safety as open surgery, and this procedure has the advantages of minimal trauma, quick recovery, and good cosmetic effect.

Single-Site Laparoscopic Percutaneous Extraperitoneal Closure of the Internal Ring Using an Epidural Needle for Children with Inguinal Hernia.

BACKGROUND This study evaluated the safety and effectiveness of single-site laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle for children with inguinal hernia. MATERIAL AND METHODS We retrospectively analyzed clinical data of 542 children with inguinal hernia who underwent single-site laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle at our hospital from June 2014 to June 2017. RESULTS All patients successfully underwent surgery and none were converted to conventional surgery. Abdominal vascular injury, vasectomy injury, testicular vascular injury, umbilical hernia, iatrogenic cryptorchidism, testicular atrophy, hydrocele, hernia recurrence, and scrotal edema were not reported during the perioperative period. A follow-up of these patients was performed for 12-24 months. During the follow-up period, umbilical hernia, iatrogenic cryptorchidism, testicular atrophy, and hydrocele were not noted, but 3 cases of hernia recurrence were found. CONCLUSIONS The single-site laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle for children with inguinal hernia is safe and effective, and this procedure has the advantages of minimal trauma, no scarring, and good cosmetic effect.

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.