A nomogram of anastomotic stricture after rectal cancer: a retrospective cohort analysis.

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

Predicting survival and prognosis in early-onset locally advanced colon cancer: a retrospective observational study.

OBJECTIVE: To predict cancer-specific survival, a refined nomogram model and brand-new risk-stratifying system were established to classify the risk levels of patients with early-onset locally advanced colon cancer (LACC). METHODS: The clinical factors and survival outcomes of LACC cases from the SEER database from 2010 to 2019 were retrieved retrospectively. Early-onset and late-onset colon cancer were grouped according to the age (50 years old) at diagnosis. Differences between groups were compared to identify mutual significant variables. A multivariate Cox regression analysis was further performed and then constructed a nomogram. We compared it with the AJCC-TNM system. The external validation was performed for evaluation. Finally, a risk-stratifying system of patients with early-onset LACC was established. RESULTS: A total of 32,855 LACC patients were enrolled in, 4548 (13.84%) patients were included in the early-onset LACC group, and 28,307 (86.16%) patients were included in the late-onset LACC group. The external validation set included 228 early-onset LACC patients. Early-onset colon cancers had poorer prognosis (T4, N2, TNM stage III, CEA, tumor deposit, and nerve invasion), and a higher proportion received radiotherapy and systemic therapy (P<0.001). In the survival analysis, cancer-specific survival (CSS) was better in patients with early-onset LACC than in those with late-onset LACC (P <0.001). This nomogram constructed based on the results of COX analysis showed better accuracy in CSS prediction of early-onset LACC patients than AJCC-TNM system in the training set and external validation set (0.783 vs 0.728; 0.852 vs 0.773). CONCLUSION: We developed a novel nomogram model to predict CSS in patients with early-onset LACC it provided a reference in prognosis prediction and selection of individualized treatment, helping clinicians in decision-making.

Surgical outcomes of laparoscopic proximal gastrectomy for upper-third gastric cancer: esophagogastrostomy, gastric tube reconstruction, and double-tract reconstruction.

BACKGROUND: There is no consensus on the optimal reconstruction technique after proximal gastrectomy. The purpose of this study was to retrospectively compare the surgical outcomes among esophagogastrostomy (EG) anastomosis, gastric tube (GT) reconstruction and double-tract (DT) reconstruction in patients who underwent laparoscopic proximal gastrectomy (LPG) to clarify the superior reconstruction method. METHODS: This study enrolled 164 patients who underwent LPG at the Northern Jiangsu People's Hospital in Jiangsu between January 2017 to January 2022 (EG: 51 patients; GT: 77 patients; DT: 36 patients). We compared the clinical and pathological characteristics, surgical features, postoperative complications, nutritional status, and quality of life (QOL) among the above three groups. RESULTS: Mean operative time was longer with the DT group than the remaining two groups (p = 0.001). With regard to postoperative complications, considerable differences in the postoperative reflux symptoms (p = 0.042) and reflux esophagitis (p = 0.040) among the three groups were found. For the nutritional status, total protein, hemoglobin and albumin reduction rates in the GT group were significantly higher than the other two groups at 12 months postoperatively. In the PGSAS-45, three assessment items were better in the DT group significantly compared with the esophageal reflux subscale (p = 0.047, Cohen's d = 0.44), dissatisfaction at the meal (p = 0.009, Cohen's d = 0.58), and dissatisfaction for daily life subscale (p = 0.012, Cohen's d = 0.56). CONCLUSIONS: DT after LPG is a valuable reconstruction technique with satisfactory surgical outcomes, especially regarding reduced reflux symptoms, improving the postoperative nutritional status and QOL.

A novel delins (c.773_819+47delinsAA) mutation of the PCCA gene associated with neonatal-onset propionic acidemia: a case report.

BACKGROUND: Propionic acidemia (PA)(OMIM#606054) is an inborn error of branched-chain amino acid metabolism, caused by defects in the propionyl-CoA carboxylase (PCC) enzyme which encoded by the PCCA and PCCB genes. CASE PRESENTATION: Here we report a Chinese neonate diagnosed with suspected PA based on the clinical symptoms, gas chromatography-mass spectrometry (GC/MS), and brain imaging tests. Targeted next-generation sequencing (NGS) was performed on the proband. We detected only one heterozygous recurrent nonsense variant (c.937C > T, p.Arg313Ter) in the PCCA gene. When we manually checked the binary alignment map (BAM) diagram of PCCA gene, we found a heterozygous deletion chr13:100915039-100915132delinsAA (c.773_819 + 47delinsAA) (GRCh37.p13) inside the exon 10 in the PCCA gene. The results were validated by Sanger sequencing and qPCR method in the family: the variant (c.937C > T, p.Arg313Ter) was in the maternal allele, and the delins was in the paternal allele. When the mother was pregnant again, prenatal diagnosis was carried out through amniocentesis at 18 weeks gestation, the fetus carried neither of the two mutations. After birth, newborn screening was undertaken, the result was negative. CONCLUSIONS: We identified a recurrent c.937C > T and a novel c.773_819 + 47delinsAA mutations in the PCCA gene, which may be the genetic cause of the phenotype of this patient. Our findings expanded the spectrum of causative genotype-phenotype of the PCCA gene. For the cases, the NGS results revealed only a heterozygous mutation in autosomal recessive disease when the gene is associated with phenotypes, it is necessary to manually check the BAM diagram to improve the detection rate. Targeted NGS is an effective technique to detect the various genetic lesions responsible for the PA in one step. Genetic testing is essential for genetic counselling and prenatal diagnosis in the family to avoid birth defects.

Novel compound heterozygous mutations in OCA2 gene associated with non-syndromic oculocutaneous albinism in a Chinese Han patient: a case report.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders. The present study aimed to identify the genetic cause of a Chinese Han family with non-syndromic oculocutaneous albinism (OCA). CASE PRESENTATION: Here, we report an 11-month-old male proband from a Chinese Han non-consanguineous family, who presented with milky skin, yellow white hair, nystagmus, astigmatism, and hypermetropia. We performed the targeted next-generation sequencing (NGS) on the proband and identified two novel compound heterozygous variants (c.1865 T > C (p.Leu622Pro) and exons 17-21 deletion) in OCA2 gene associated with OCA type 2 (OCA2, OMIM 203200). Meanwhile, a previously reported heterozygous mutation (c.4805G > A) in MYO7 gene related with Usher syndrome type 1B was found. The online tools SIFT, PolyPhen-2, and Mutation Taster predicted variant c.1865 T > C was probably damaging. The residue p.Leu622 was in a highly conserved region among species by CLUSTALW. Three-dimensional homology model with I-TASSER indicated that p.Leu622Pro variant disturbed the formation of the α-helix, resulting in a random coil structure. The gross deletion (exons 17-21) in OCA2 gene has was not been reported previously. These two novel variants in OCA2 gene were inherited from each parent respectively, after verification by Sanger sequencing and quantitative PCR (qPCR) in the family. CONCLUSIONS: This study indicates the two novel compound heterozygous mutations in OCA2 gene may be responsible for clinical manifestations of OCA2. It expands the mutation spectrum of OCA2 gene and is helpful to screen for large deletions with targeted NGS protocol in monogenic disease. It also assists the genetic counselling, carrier screening and personalized healthcare of the disease.

A Malicious Behavior Awareness and Defense Countermeasure Based on LoRaWAN Protocol.

Low power wide area network (LoRaWAN) protocol has been widely used in various fields. With its rapid development, security issues about the awareness and defense against malicious events in the Internet of Things must be taken seriously. Eavesdroppers can exploit the shortcomings of the specification and the limited consumption performance of devices to carry out security attacks such as replay attacks. In the process of the over-the-air-activation (OTAA) for LoRa nodes, attackers can modify the data because the data is transmitted in plain text. If the user's root key is leaked, the wireless sensor network will not be able to prevent malicious nodes from joining the network. To solve this security flaw in LoRaWAN, we propose a countermeasure called Secure-Packet-Transmission scheme (SPT) which works based on the LoRaWAN standard v1.1 to prevent replay attacks when an attacker has obtained the root key. The proposed scheme redefines the format of join-request packet, add the new One Time Password (OTP) encrypted method and changes the transmission strategy in OTAA between LoRa nodes and network server. The security evaluation by using the Burrows-Abadi-Needham logic (BAN Logic) and the Scyther shows that the security goal can be achieved. This paper also conducts extensive experiments by simulations and a testbed to perform feasibility and performance analysis. All results demonstrate that SPT is lightweight, efficient and able to defend against malicious behavior.

Development and Characterization of the Shale Stratum Well Wall Stabilized with Nanosomal Sealing Agent.

The development of micro cracks in shale formations can easily lead to wellbore instability caused by liquid phase invasion. In order to effectively seal the shale micropores, the surface treatment of nano-SiO2 particles was developed using the silicane coupling agent A-1891. Then, the temperature-sensitive polypenic acrylamide polymer was modified onto the surface of the nanoprocal particle through reaction to obtain the nanosomal blocking agent ASN. The infrared spectrum shows that there are chemical bonds between the generated polymer chains, rather than simple physical composites, indicating the successful synthesis of the temperature-responsive nanosealing agent ASN. The particle size analysis showed that the synthesized nanoparticles in ASN have a uniform particle size distribution and display no agglomeration phenomenon. Applying ASN as a sealing agent in drilling fluid effectively fills the nanoscale micropores and microcracks in shale, making shale denser and significantly improving the wellbore stability of shale formations. In addition, it has good temperature resistance, can adapt to reservoirs at different temperatures, is non-toxic and environmentally friendly, and has good prospects for stable applications in shale formation wellbore.

PLCD3 inhibits apoptosis and promotes proliferation, invasion and migration in gastric cancer.

Gastric cancer (GC) is a heterogeneous disease whose development is accompanied by alterations in a variety of pathogenic genes. The phospholipase C Delta 3 enzyme is a member of the phospholipase C family, which controls substance transport between cells in the body. However, its role in gastric cancer has not been discovered. The purpose of this study was to investigate the expression and mechanism of action of PLCD3 in connection to gastric cancer. By Western blot analysis and immunohistochemistry, PLCD3 mRNA and protein expression levels were measured, with high PLCD3 expression suggesting poor prognosis. In N87 and HGC-27 cells, the silencing of PLCD3 using small interfering RNA effectively induced apoptosis and inhibited tumor cell proliferation, invasion, and migration. Conversely, overexpression of PLCD3 using overexpressed plasmids inhibited apoptosis in AGS and BGC-823 cells and promoted proliferation, migration, and invasion. In order to investigate the underlying mechanisms, we conducted further analysis of PLCD3, which indicates that this protein is closely related to the cell cycle and EMT. Additionally, we found that overexpression of PLCD3 inhibits apoptosis and promotes the development of GC cells through JAK2/STAT3 signaling. In conclusion, PLCD3 inhibits apoptosis and promotes proliferation, invasion, and migration, which indicated that PLCD3 might serve as a therapeutic target for gastric cancer.

Development of a model based on the age-adjusted Charlson comorbidity index to predict survival for resected perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) has a poor prognosis and urgently needs a better predictive method. The predictive value of the age-adjusted Charlson comorbidity index (ACCI) for the long-term prognosis of patients with multiple malignancies was recently reported. However, pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis, and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear. AIM: To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients. METHODS: Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database. The patients were randomly assigned 3:1 to training and validation cohorts. In the training and validation cohorts, all patients were divided into low-, moderate-, and high-ACCI groups. Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival (OS) for pCCA patients, and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS. An online clinical model based on the ACCI was developed and validated. The concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance and fit of this model. RESULTS: A total of 325 patients were included. There were 244 patients in the training cohort and 81 patients in the validation cohort. In the training cohort, 116, 91 and 37 patients were classified into the low-, moderate- and high-ACCI groups. The Kaplan-Meier curves showed that patients in the moderate- and high-ACCI groups had worse survival rates than those in the low-ACCI group. Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection. In addition, an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts. The calibration curve and ROC curve indicated that the model had a good fit and prediction performance. CONCLUSION: A high ACCI score may predict poor long-term survival in pCCA patients after curative resection. High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.

Assessment of the prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in perihilar cholangiocarcinoma patients following curative resection: A multicenter study of 333 patients.

Background & Aims: Tumor-associated chronic inflammation has been determined to play a crucial role in tumor progression, angiogenesis and immunosuppression. The objective of this study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in perihilar cholangiocarcinoma (pCCA) patients following curative resection. Methods: Consecutive pCCA patients following curative resection at 3 Chinese hospitals between 2014 and 2018 were included. The NLR was defined as the ratio of neutrophil count to lymphocyte count. PLR was defined as the ratio of platelet count to lymphocyte count. The optimal cutoff values of preoperative NLR and PLR were determined according to receiver operating characteristic (ROC) curves for the prediction of 1-year overall survival (OS), and all patients were divided into high- and low-risk groups. Kaplan-Meier curves and Cox regression models were used to investigate the relationship between values of NLR and PLR and values of OS and recurrence-free survival (RFS) in pCCA patients. The usefulness of NLR and PLR in predicting OS and RFS was evaluated by time-dependent ROC curves. Results: A total of 333 patients were included. According to the ROC curve for the prediction of 1-year OS, the optimal cutoff values of preoperative NLR and PLR were 1.68 and 113.1, respectively, and all patients were divided into high- and low-risk groups. The 5-year survival rates in the low-NLR (<1.68) and low-PLR groups (<113.1) were 30.1% and 29.4%, respectively, which were significantly higher than the rates of 14.9% and 3.3% in the high-NLR group (≥1.68) and high-PLR group (≥113.1), respectively. In multivariate analysis, high NLR and high PLR were independently associated with poor OS and RFS for pCCA patients. The time-dependent ROC curve revealed that both NLR and PLR were ideally useful in predicting OS and RFS for pCCA patients. Conclusions: This study found that both NLR and PLR could be used to effectively predict long-term survival in patients with pCCA who underwent curative resection.

Impact of degree heterogeneity on the behavior of trapping in Koch networks.

Previous work shows that the mean first-passage time (MFPT) for random walks to a given hub node (node with maximum degree) in uncorrelated random scale-free networks is closely related to the exponent γ of power-law degree distribution P(k) ∼ k(-γ), which describes the extent of heterogeneity of scale-free network structure. However, extensive empirical research indicates that real networked systems also display ubiquitous degree correlations. In this paper, we address the trapping issue on the Koch networks, which is a special random walk with one trap fixed at a hub node. The Koch networks are power-law with the characteristic exponent γ in the range between 2 and 3, they are either assortative or disassortative. We calculate exactly the MFPT that is the average of first-passage time from all other nodes to the trap. The obtained explicit solution shows that in large networks the MFPT varies lineally with node number N, which is obviously independent of γ and is sharp contrast to the scaling behavior of MFPT observed for uncorrelated random scale-free networks, where γ influences qualitatively the MFPT of trapping problem.

A Heterozygous Novel Mutation in TFAP2A Gene Causes Atypical Branchio-Oculo-Facial Syndrome With Isolated Coloboma of Choroid: A Case Report.

Background: Branchio-oculo-facial syndrome (BOFS) is a rare congenital developmental disorder with highly variable clinical phenotypes in autosomal dominant inheritance. The aim of this study is to identify disease-causing mutations in a Chinese family with predominant coloboma of choroid. Case report: We described a family (a mother and her daughter) with unclear clinical diagnosis. The mother (proband) presented with bilateral coloboma of choroid, whereas her daughter had a relatively severe phenotype and presented with larger bilateral choroid coloboma and high-vaulted arch. We applied the next generation sequencing (NGS) panel and analyzed 776 genes related to inherited ocular disorders on the proband. Four candidate heterozygous variants in four genes, respectively, were detected in the proband. Validation of these variants were subsequently performed in the family using Sanger sequencing. Among these variants, a novel nonsense mutation c.912C>A, p.(Cys304*) (NM_001042425.2) which in exon 6 of the conserved helix-span-helix domain in TFAP2A results in a premature termination codon. It may trigger nonsense-mediated mRNA decay (NMD). Both the affected mother and daughter had this variant, whereas it was absent in the asymptomatic father. Together with the silicon tools and clinical features, we concluded that the variant c.912C>A, p.(Cys304*), was the second reported nonsense mutation in TFAP2A gene, which was the disease-causing mutation of the family. Conclusion: There are many hereditary diseases accompanied by ocular anomalies. For instance, BOFS, patients with atypical features are always at risk of being under-diagnosed. NGS is a powerful method to identify the genetic cause and improve genetic counseling for less clarified hereditary ocular diseases.

Targeted next-generation sequencing identifies a novel mutation of LAMB3 in a Chinese neonatal patient presented with junctional epidermolysis bullosa.

RATIONALE: Epidermolysis bullosa (EB) refers to a group of rare inherited mechanobullous disorders that present with great clinical and genetic heterogeneity. Its severity ranges from mild blistering to life-threatening. However, the clinical symptoms of different types of EB overlap significantly, especially at an early stage. Thus it is important to clarify the diagnosis for prognostic implications, patient management, and genetic counseling. PATIENT CONCERNS: Here, we report a 10-day-old male neonate from a nonconsanguineous Chinese family. He showed a bulla on the left lower limb lasting for 3 days, erosions around fingertips and toe tips at birth (predominantly on fingers), with the progressive spread of generalized blisters over the body as well as the development of the illness. DIAGNOSIS: The patient was diagnosed with suspected epidermolysis bullosa according to the blisters and erosions of the body as well as the pyogenic fingernails and toenails. INTERVENTIONS: The patient was performed targeted next-generation sequencing (NGS) with 9 candidate known genes, subsequently, his parents were screened for the mutations identified in the patient by Sanger sequencing. Then, prenatal diagnosis with amniotic fluid was performed in the subsequent pregnancy by Sanger sequencing. OUTCOMES: Targeted NGS revealed a previously unreported splice site variant c.822+1G>A (IVS 8) and a known recurrent nonsense variant c.124C>T (p.Arg42Ter, exon 3) in LAMB3 gene. The patient's father possessed a heterozygous c.822+1G>A mutation, his mother possessed a heterozygous c.124C>T mutation. For the subsequent pregnancy, the analyses of amniotic fluid sample indicated that the fetus carried neither of the mutations. LESSONS: Our finding will further enlarge LAMB3 genotype-phenotype correlations spectrum. Targeted capture sequencing is a valuable method to illustrate precise molecular pathology in patients with EB disorders, especially at an early stage of the clinical evaluation of complex disorders to avoid unnecessary and economically wasteful tests.

Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach.

We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect--length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors.

Explicit determination of mean first-passage time for random walks on deterministic uniform recursive trees.

The determination of mean first-passage time (MFPT) for random walks in networks is a theoretical challenge, and is a topic of considerable recent interest within the physics community. In this paper, according to the known connections between MFPT, effective resistance, and the eigenvalues of graph Laplacian, we first study analytically the MFPT between all node pairs of a class of growing treelike networks, which we term deterministic uniform recursive trees (DURTs), since one of its particular cases is a deterministic version of the famous uniform recursive tree. The interesting quantity is determined exactly through the recursive relation of the Laplacian spectra obtained from the special construction of DURTs. The analytical result shows that the MFPT between all couples of nodes in DURTs varies as N ln N for large networks with node number N. Second, we study trapping on a particular network of DURTs, focusing on a special case with the immobile trap positioned at a node having largest degree. We determine exactly the average trapping time (ATT) that is defined as the average of FPT from all nodes to the trap. In contrast to the scaling of the MFPT, the leading behavior of ATT is a linear function of N. Interestingly, we show that the behavior for ATT of the trapping problem is related to the trapping location, which is in comparison with the phenomenon of trapping on fractal T-graph although both networks exhibit tree structure. Finally, we believe that the methods could open the way to exactly calculate the MFPT and ATT in a wide range of deterministic media.

Trapping in scale-free networks with hierarchical organization of modularity.

A wide variety of real-life networks share two remarkable generic topological properties: scale-free behavior and modular organization, and it is natural and important to study how these two features affect the dynamical processes taking place on such networks. In this paper, we investigate a simple stochastic process--trapping problem, a random walk with a perfect trap fixed at a given location, performed on a family of hierarchical networks that exhibit simultaneously striking scale-free and modular structure. We focus on a particular case with the immobile trap positioned at the hub node having the largest degree. Using a method based on generating functions, we determine explicitly the mean first-passage time (MFPT) for the trapping problem, which is the mean of the node-to-trap first-passage time over the entire network. The exact expression for the MFPT is calculated through the recurrence relations derived from the special construction of the hierarchical networks. The obtained rigorous formula corroborated by extensive direct numerical calculations exhibits that the MFPT grows algebraically with the network order. Concretely, the MFPT increases as a power-law function of the number of nodes with the exponent much less than 1. We demonstrate that the hierarchical networks under consideration have more efficient structure for transport by diffusion in contrast with other analytically soluble media including some previously studied scale-free networks. We argue that the scale-free and modular topologies are responsible for the high efficiency of the trapping process on the hierarchical networks.