Balanced opioid-free anesthesia with lidocaine and esketamine versus balanced anesthesia with sufentanil for gynecological endoscopic surgery: a randomized controlled trial.

In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 µg/kg) and saline, followed by sufentanil (0.1 µg/kg∙h) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kg∙h) and lidocaine (1.5 mg/kg∙h). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06-1.58) and 1.09 (0.70) (95% CI 0.87-1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was - 0.23 (95% CI - 0.58 - 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.

Unraveling the tumor immune microenvironment of lung adenocarcinoma using single-cell RNA sequencing.

Tumor immune microenvironment (TIME) and its indications for lung cancer patient prognosis and therapeutic response have become new hotspots in cancer research in recent years. Tumor cells, immune cells, various regulatory factors, and their interactions in the TIME have been suggested to commonly influence lung cancer development and therapeutic outcome. The heterogeneity of TIME is composed of dynamic immune-related components, including various cancer cells, immune cells, cytokine/chemokine environments, cytotoxic activity, or immunosuppressive factors. The specific composition of cell subtypes may facilitate or hamper the response to immunotherapy and influence patient prognosis. Various markers have been found to stratify the patient prognosis or predict the therapeutic outcome. In this article, we systematically reviewed the recent advancement of TIME studies in lung adenocarcinoma (LUAD) using single-cell RNA sequencing (scRNA-seq) techniques, with specific focuses on the roles of TIME in LUAD development, TIME heterogeneity, indications of TIME in patient prognosis and therapeutic response during immunotherapy and drug resistance. The main findings in TIME heterogeneity and relevant markers or models for prognosis stratification and response prediction have been summarized. We hope that this review provides an overview of TIME status in LUAD and an inspiration for future development of strategies and biomarkers in LUAD treatment.

50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

A Meta-Analysis for Postoperative Alternations of Aortic Coarctation.

OBJECTIVE: To investigate postoperative vascular changes of patients with coarctation of the aorta (CoA). METHODS: Literature review of updated articles was performed in June 2023 through the following databases: PubMed, Web of Science, EMBASE, Crohrane Library, CNKI and Wanfang database. All the case-control studies regarding the postoperative changes of vascular structure and function in patients with CoA were analyzed. RESULTS: A total of 596 articles from the above databases were initially identified, with 10 articles being selected for meta-analysis. The analysis showed that weighted mean difference (WMD) of carotid intima-media thickness (cIMT) was 0.07 (95% CI = 0.01~0.13, p < 0.01) and WMD of flow mediated dilation (FMD) was -4.36 (95% CI = -7.49~-1.24, p < 0.01), respectively. The postoperative cIMT of CoA patients was higher than that of the control group, but the postoperative FMD was lower than that of the control group. CONCLUSIONS: The operation on CoA patients ameliorates anatomical deformity in the vascular structures. However, intima-media thickening and endothelial malfunction remain as the key postoperative issues.

Multi-omics analysis reveals the molecular basis of flavonoid accumulation in fructus of Gardenia (Gardenia jasminoides Ellis).

BACKGROUND: The fruits of Gardenia are rich in flavonoids and geniposides, which have various pharmacological effects such as antioxidant, anti-inflammatory and anticancer. In this study, we analyzed the transcriptome and metabolome of gardenia peel and kernel at different growth stages, revealed the regulatory network related to flavonoid synthesis, and identified the key regulatory genes. RESULTS: The results showed that in terms of flavonoid metabolic pathways, gardenia fruits mainly synthesized cinnamic acid through the phenylpropanoid pathway, and then synthesized flavonoids through the action of catalytic enzymes such as 4-coumaroyl-CoA ligase, chalcone synthase, chalcone isomerase and flavanol synthase, respectively. In addition, we found that the metabolomics data showed a certain spatial and temporal pattern in the expression of genes related to the flavonoid metabolism pathway and the relative content of metabolites, which was related to the development and ripening process of the fruit. CONCLUSIONS: In summary, this study successfully screened out the key genes related to the biosynthesis metabolism of flavonoids in gardenia through the joint analysis of transcriptome and metabolome. This is of certain significance to the in-depth study of the formation mechanism of gardenia efficacy components and the improvement of quality.

Development and Optimization of A Human Hepatocellular Carcinoma Patient-Derived Organoid Model for Potential Target Identification and Drug Discovery.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents necessitate further research into its pathogenesis and treatment. Organoids, a novel model that closely resembles native tumor tissue and can be cultured in vitro, have garnered significant interest in recent years, with numerous reports on the development of organoid models for liver cancer. In this study, we have successfully optimized the procedure and established a culture protocol that enables the formation of larger-sized HCC organoids with stable passaging and culture conditions. We have comprehensively outlined each step of the procedure, covering the entire process of HCC tissue dissociation, organoid plating, culture, passaging, cryopreservation, and resuscitation, and provided detailed precautions in this paper. These organoids exhibit genetic similarity to the original HCC tissues and can be utilized for diverse applications, including the identification of potential therapeutic targets for tumors and subsequent drug development.

Opioid-free anesthesia with lidocaine for improved postoperative recovery in hysteroscopy: a randomized controlled trial.

BACKGROUND: Anesthesia with opioids negatively affects patients' quality of recovery. Opioid-free anesthesia attempts to avoid these effects. This study aimed to evaluate the effect of opioid-free anesthesia on the quality of recovery, using lidocaine on patients undergoing hysteroscopy. METHODS: A parallel-group, randomized, double-blind, controlled trial was conducted in Yichang Central Peoples' Hospital, Hubei Province, China, from January to April, 2022. We included 90 female patients (age: 18-65 years, American Society of Anesthesiologists Physical Status Class I-II) scheduled for elective hysteroscopy, 45 of whom received lidocaine (Group L), and 45 received sufentanil (Group S). Patients were randomly allocated to receive either lidocaine or sufentanil perioperatively. The primary outcome was the quality of postoperative recovery, which was assessed using the QoR-40 questionnaire (a patient-reported outcome questionnaire measuring the quality of recovery after surgery). RESULTS: The two groups were similar in age, American Society of Anesthesiology physical status, height, weight, body mass index, and surgical duration. The QoR scores were significantly higher in Group L than Group S. The incidence of postoperative nausea and vomiting, as well as the time to extubation were significantly lower in Group L than Group S. CONCLUSION: Opioid-free anesthesia with lidocaine achieves a better quality of recovery, faster recovery, and a shorter time to extubation than general anesthesia with sufentanil. TRIAL REGISTRATION: The trial was registered on January 15, 2022 in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showprojen.aspx?proj=149386 ), registration number ChiCTR2200055623.(15/01/2022).

The Natural Alkaloid (-)-N-Hydroxyapiosporamide Suppresses Colorectal Tumor Progression as an NF-κB Pathway Inhibitor by Targeting the TAK1-TRAF6 Complex.

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.

Thoracoscopic surgery for congenital diaphragmatic hernia in neonates: Should it be the first choice?

Objective: Congenital diaphragmatic hernia (CDH) is an uncommon but potentially life-threatening surgical condition in neonates. Surgery can be performed by either open or thoracoscopic techniques. In this study, we compared the clinical efficacy, safety, and effectiveness of thoracoscopic and open CDH repair. Methods: A retrospective review of neonates with CDH who underwent operations at our hospital from 2013 to 2021 was performed. The various perioperative parameters were compared between neonates undergoing thoracoscopic and open surgery. Results: There were 50 neonates in this study (37 in the thoracoscopic group and 13 in the open group). Thoracoscopic surgery was associated with significantly shorter hospital stay (13.32 vs. 18.77 days, p < 0.001); shorter duration of postoperative mechanical ventilation (3.70 vs. 5.98 days, p < 0.001); early feeding (4.34 vs. 7.46 days, p < 0.001); and shorter time to reach optimal feeding (8.21 vs. 13.38 days, p < 0.001). There was one postoperative death in the open group and no death in the thoracoscopic group. The median follow-up time of the two groups was 23.8 months (20.5 months in open group and 25.0 months in thoracoscopic group). Thoracoscopic surgery was associated with lower recurrence rates, but the difference was not statistically significant (2.7% vs. 7.7%, p = 0.456). Conclusion: Thoracoscopy CDH repair, a safe and effective surgical technique for neonates, has better cosmesis, faster postoperative recovery, and a lower recurrence rate than other procedures. It can be considered the first choice for CDH treatment for neonates among experienced surgeons.

MAL31, a sugar transporter involved in pullulan biosynthesis in Aureobasidium pullulans.

To investigate the role of the sugar transporter MAL31 on pullulan biosynthesis, the coding gene mal31 was respectively disrupted and overexpressed in the parental strain A. pullulans CCTCC M 2012259 to construct mutants of A. pullulans Δmal31 and A. pullulans Mal31. Batch pullulan production significantly decreased by 69.1 % in A. pullulans Δmal31 but increased by 15.9 % in A. pullulans Mal31, as compared to the parental strain. We performed kinetics analysis, assays of key enzymes, determination of intracellular UDPG, NADH, and ATP contents, and measurement of transcriptional levels of genes associated with pullulan biosynthesis and excretion. The results confirmed that the mal31 disruption decreased the glucose consumption rate, decreased the formation rate and titer of pullulan, but increased the intracellular UDPG supply for ß-glucan accumulation. In contrast, the mal31 overexpression increased the transcriptional levels of genes associated with pullulan biosynthesis, and accelerated the rates of glucose consumption and pullulan formation, thereby increased pullulan production. Our findings revealed that MAL31 is involved in the transport of precursors for pullulan biosynthesis. This study provides an accurate operating site for genetic modification of A. pullulans for improving pullulan production and also presents a feasible technique route for the overproduction of other polysaccharides.

Intravenous lidocaine on postoperative pain and opioid consumption during gynecological surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to evaluate the role of intravenous lidocaine as a adjuvant anesthetics in patients undergoing gynecological surgery. EVIDENCE ACQUISITION: We conducted a meta-analysis of randomized controlled trials (RCTs) from PUMED/MELINE, EMBASE and clinic trails.gov involving the use of intravenous lidocaine in gynecological surgery. We used a more comprehensive search strategy to adequately screen for randomized controlled trials involving intravenous lidocaine infusion in gynecological surgery. First outcomes were postoperative pain scores. And secondary outcomes included 24 h postoperative opioids consumption, time to first flatus, and incidence of postoperative nausea and vomiting. EVIDENCE SYNTHESIS: A total of 6 RCTs comprising 375 patients were included in the meta-analysis. There were statistically significant between postoperative pain scores. The consumption of opioids and anesthetics during surgery and 24 hours after surgery was statistically significant when compared with the control group. Postoperative pain scores were similar at 2,4,6,8,10,12,24,48 hour between groups. No statistical differences were found in postoperative complications including nausea, vomiting and restoration of the intestinal function. CONCLUSIONS: Our results indicated that the current literature supports the perioperative use of intravenous lidocaine as part of multimodal analgesia and beneficial to patients in early postoperative analgesia, reduced opioid consumption.

Single-cell transcriptome sequencing reveals potential novel combination of biomarkers for antibody-based cancer therapeutics in hepatocellular carcinoma.

Background: Antibody-based cancer therapeutics is developing rapidly in recent years for its advantages in precisely targeting the tumor cells. However, tumor-specific cell surface antigens are still lacking, and the heterogeneity of tumor mass greatly impeded the development of effective drugs. Methods: In the present study, single-cell RNA sequencing was used to dissect tumor heterogeneity in human hepatocellular carcinoma (HCC). Tissues from different spatial regions including the tumor, para-tumor, and distant normal liver tissues were dissociated into single cells, and the gene expressions were compared in a different subpopulation of cells from these regions and validated in independent cohorts. Results: A total of 28 cell clusters with different distribution patterns and gene expression profiles were identified within a heterogenous tumor and its paired liver tissues. Differentially expressed genes encoding the plasma membrane in cells with hepatic lineage were further extracted from single-cell transcriptome sequencing and validated in TCGA database. A 3-gene signature was identified to be significantly upregulated in dominant HCC tumor cell subpopulations with prognostic significance and validated in multiple independent patient cohorts. Conclusion: The composition of the three plasma membrane proteins on the surface of HCC tumor cells within a heterogenous tumor might indicate poor prognostic tumor subpopulations during cancer evolution and potential therapeutic targets.

The ryanodine receptor mutational characteristics and its indication for cancer prognosis.

Ca2+ signaling is altered substantially in many cancers. The ryanodine receptors (RYRs) are among the key ion channels in Ca2+ signaling. This study aimed to establish the mutational profile of RYR in cancers and investigate the correlation between RYR alterations and cancer phenotypes. The somatic mutation and clinical data of 11,000 cancer patients across 33 cancer types was downloaded from The Cancer Genome Atlas (TCGA) database. Subsequent data processing was performed with corresponding packages of the R software. Mutational profile was analyzed and its correlation with tumor mutational burden (TMB), patient prognosis, age and smoking status was analyzed and compared. All three RYR isoforms exhibited random mutational distribution without hotspot mutations when all cancers were analyzed together. The number of mutations in RYR2 (2388 mutations) far overweight that of RYR1 (1439 mutations) and RYR3 (1573 mutations). Linear correlation was observed between cumulative TMB and cumulative number of mutations for all RYR isoforms. Patients with RYR mutations exhibited significantly higher TMB than those without RYR mutations for most cancer types. Strong correlation was also revealed in the average number of mutations per person between pairs of RYR isoforms. No stratification of patient overall survival (OS) by mutational status was found for all three RYR isoforms when all cancers were analyzed together, however, significant stratification of OS by RYR mutations was revealed in several individual cancers, most strikingly in LUAD (P = 0.0067, RYR1), BLCA (P = 0.00071, RYR2), LUSC (P = 0.036, RYR2) and KIRC (P = 0.0042, RYR3). Furthermore, RYR mutations were correlated with higher age, higher smoking history grading and higher number of pack years. Characteristic mutation profile of RYRs in cancers has been revealed for the first time. RYR mutations were correlated with TMB, age, smoking status and capable of stratifying the prognosis of patients in several cancer types.

Gastric cancer cell-derived extracellular vesicles disrupt endothelial integrity and promote metastasis.

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.

The Radiographic Changes of Catheter Tip in Different Positions of Arm Infusion Port.

In order to investigate the influence of patient position change on the position of catheter tip in arm infusion port, the clinical data of 324 patients undergoing arm infusion port implantation in a hospital were retrospectively analyzed. It could be obtained that TIVAP was successfully implanted in 324 patients with malignant tumors. In 171 cases, the TIVAP catheter tip shifted to the foot side when the position was changed from upright to decubitus, with an average displacement of (12.29 ± 7.48) mm; 149 cases had cephalic displacement with an average of (5.00 ± 3.79) mm; and 5 cases had no change. The position of the TIVAP catheter tip tended to shift to the foot side when the vertical position changed to the decubitus position, with an average displacement of (-9.32 ± 9.36) mm, and the difference had statistical significance (P < 0.0001), while there were no significant differences in gender, age, height, weight, body mass index, and catheter tip position (P > 0.05). It could be analyzed from the data that from decubitus to upright position, the tip of the arm infusion port tended to shift to the foot side, and the moving distance was related to the patient's gender, sebum thickness, and indwelling catheter length. Preoperative understanding of relevant information is helpful to determine the location and length of catheterization and reduce catheter-related complications.

Reduced Incidence of Necrotizing Enterocolitis due to the Anti-Inflammatory Effects of CXCL14 in Intestinal Tissue.

Bioinformatic analysis indicated that downregulated CXCL14 will occur in the intestinal tissue of patients with necrotizing enterocolitis (NEC). To reveal the relationship between CXCL14 and mucosal immune regulation, we designed and implemented the experiments to explore the potential function of CXCL14 in the pathogenesis of NEC. Firstly, this study confirmed that the expression of CXCL14 decreased in the intestinal tract of NEC children. Secondly, the experiments results showed that CXCL14 could ameliorate the inflammatory injury of intestinal tissue through the suppressive effect on the expression of TNF-α and INF-γ in vivo. Finally, we explained that activation of the TLR4 can reduce the expression level of CXCL14 in the intestinal tissue of mouse pups. Collectively, our study suggested that CXCL14 may negatively regulate the inflammatory response in intestinal tissue and play an essential role in NEC development and progression.

Laparoscopic Complete Excision of the Posterior Muscular Cuff: Technique Refinements and Comparison With Stepwise Gradient Muscular Cuff Cutting for Hirschsprung Disease.

Objectives: Our institution had modified the Soave pull-through procedure using laparoscopic stepwise gradient muscular cuff cutting (LSGC) for Hirschsprung disease (HSCR). However, we found that a few children still suffered from obstructive symptoms and enterocolitis during the follow-up. Previous studies suggested that these symptoms might be caused by the retained muscular cuff. The purpose of this study was to employ a modified procedure of laparoscopic complete excision of the posterior muscular cuff (LCEPC) for HSCR and compare it with the laparoscopic stepwise gradient cutting muscular cuff (LSGC) procedure. Methods: Our institution records of 83 patients with classic form HSCR who underwent LSGC or LCEPC between August 2014 and July 2018 at the Pediatric Surgery Department of Zunyi Medical University (Zunyi, China) were carefully reviewed (LSGC, n = 52; LCEPC, n = 31). In the present study, we compared the postoperative complications and defecation functions of the two groups. All patients were followed-up (1-5 years, with an average of 2 years). Results: There were no differences regarding the operation time and the length of hospitalization between groups, while the anal dissection time in the LCEPC group (22.4 ± 4.8 min) was shorter than that of the LSGC group (45.5 ± 7.5 min) (p < 0.001). The postoperative complication of soiling was significantly increased in six patients (19.4%) in the LCEPC group compared with two patients (3.8%) in the LSGC group (p = 0.021). However, the total incidence of enterocolitis (two patients, 6.5%) was significantly decreased in the LCEPC group compared with the LSGC group (12 patients, 23.1 %) (p = 0.050). For anastomotic stricture, muscular cuff infection, and constipation, there were no significant differences between the two groups. No patients experienced bladder paralysis and incontinence postoperatively in this study. Anorectal manometries presented that the anorectal resting pressure was significantly lower in the LCEPC group (14.8 ± 2.7 mmHg) than the LSGC group (22.0 ± 3.8 mmHg), (p < 0.001). Conclusion: The laparoscopic complete excision of the posterior muscular cuff method was demonstrated as safe and efficient, with a decrease in the incidence of enterocolitis, although it may increase the number of soiling incidents in the short period post-surgery owing to a dissected partial internal anal sphincter.

Comparison of Hand-Sewn with Stapled Anastomosis in Neonatal Intestinal Atresia Surgery: A Randomized Controlled Study.

Objective: The purpose of this study was to compare the safety and efficacy of hand-sewn versus stapled anastomosis therapy in intestinal atresia neonatal patients. Materials and Methods: This was a prospective randomized controlled trial in which 90 neonates with intestinal atresia were randomly divided into the hand-sewn group and the stapled group. All patients were assigned to undergo intestinal anastomosis by hand-sewn or stapler. The primary outcome measure was to analyze the anastomotic complications between groups. The secondary outcome measures were operative time, blood loss, length to initial feeds, length to full feeds, length of hospital stay, the incidence of bowel obstruction, reoperation and mortality, and weight and height 1 year after operation. Results: A total of 82 patients were included (43 for hand-sewn and 39 for stapled group) for primary analysis. A total of 16 patients suffered from anastomotic complications in both groups. The incidence rate of anastomotic complications in the stapled group was significantly lower than that of the hand-sewn group (27.9% versus 10.3%, P = .044). There were no differences in anastomotic leak, stricture, and bleeding in the hand-sewn group compared with stapled group. The operative time in the hand-sewn group was longer than the stapled group (P < .001), the length to initial and full feeds in the stapled group was shorter than that of the hand-sewn group (P < .001). The length of hospital stay was significantly shorter in the stapled group than the hand-sewn group (P = .016). The bowel obstruction, reoperation, weight and height, and mortality had no differences between groups during follow-up. Conclusion: Study results demonstrate that stapled anastomosis is safe and effective for intestinal atresia with distal diameter >1 cm, as it can decrease the incidence of anastomotic complications. However, the risk of anastomotic failure should be considered among type III b atresia. Clinical Trial Registration number: NCT03754907.

Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population.

OBJECTIVE: Hereditary colorectal cancer (CRC) accounts for approximately 5%-10% of all CRC cases. The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population. METHODS: We performed the first population study investigating the germline mutation status in more than 1,000 (n = 1,923) Chinese patients with CRC and examined their relationship with the somatic mutational landscape. Germline alterations were examined with a 58-gene next-generation sequencing panel, and somatic alterations were examined with a 605-gene panel. RESULTS: A total of 92 pathogenic (P) mutations were identified in 85 patients, and 81 likely pathogenic (LP) germline mutations were identified in 62 patients, accounting for 7.6% (147/1,923) of all patients. MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups, respectively. Patients with P/LP mutations had a significantly higher ratio of microsatellite instability, highly deficient mismatch repair, family history of CRC, and lower age. The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group. The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the non-Lynch syndrome group. Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Population risk analysis indicated that the overall odds ratio was 11.13 (95% CI: 8.289-15.44) for the P group and 20.68 (95% CI: 12.89-33.18) for the LP group. CONCLUSIONS: Distinct features were revealed in Chinese patients with CRC with germline mutations. The Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Patients with P/LP germline mutations exhibited higher CRC risk.