Genetics, structure, transmission, epidemiology, immune response, and vaccine efficacies of the SARS-CoV-2 Delta variant: A comprehensive review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) was the predominant variant behind the surges of COVID-19 in the United States, Europe, and India in the second half of 2021. The information available regarding the defining mutations and their effects on the structure, transmission, and vaccine efficacy of SARS-CoV-2 is constantly evolving. With waning vaccine immunity and relaxation of social distancing policies across the globe driving the increased spread of the Delta variant, there is a great need for a resource aggregating the most recent information for clinicians and researchers concerning the Delta variant. Accordingly, this narrative review comprehensively reviews the genetics, structure, epidemiology, clinical course, and vaccine efficacy of the Delta variant. Comparison with the omicron variant is also discussed. The Delta variant is defined by 15 mutations in the Spike protein, most of which increase affinity for the ACE-2 receptor or enhance immune escape. The Delta variant causes similar symptoms to prototypical COVID-19, but it is more likely to be severe, with a greater inflammatory phenotype and viral load. The reproduction number is estimated to be approximately twice the prototypical strains present during the early pandemic, and numerous breakthrough infections have been reported. Despite studies demonstrating breakthrough infection and reduced antibody neutralisation, full vaccination effectively reduces the likelihood of severe illness and hospitalisation.

A Randomized, Double-Blind, Controlled Trial of Percutaneous Tibial Nerve Stimulation With Pelvic Floor Exercises in the Treatment of Childhood Constipation.

INTRODUCTION: The management of childhood constipation is challenging. Pelvic floor dysfunction (PFD) is one of the most common causes of childhood constipation. Percutaneous tibial nerve stimulation (PTNS) with pelvic floor exercises (PFE) has achieved a satisfactory outcome in the elderly individuals and women with PFD. The efficacy of PTNS with PFE in childhood constipation has not been established. METHODS: A randomized, double-blind, controlled trial with 84 children who met the inclusion criteria was conducted. All participants were randomly assigned to PTNS with PFE or sham PTNS with PFE groups and received their individual intervention for 4 weeks with a 12-week follow-up evaluation. The spontaneous bowel movements (SBM) ≥3 per week were the main outcomes, and the risk ratio (RR) with 95% confidence interval (CI) were calculated. High-resolution anorectal manometry and surface electromyography were used for the assessment of pelvic floor function, and the adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 26 patients (61.9%) in the PTNS with PFE group and 15 patients (35.7%) in the sham group had ≥3 SBM per week compared with baseline (net difference 26.2%, 95% CI 5.6%-46.8%; RR 2.750, 95% CI 1.384-5.466; P < 0.05). PFD remission occurred in 49 children, 33 (78.6%) in the PTNS with PFE group and 16 (38.1%) in the sham group (RR 2.063, 95% CI 1.360-3.128, P < 0.05). No adverse effects occurred. DISCUSSION: PTNS with PFE is a safe and effective method in the treatment of childhood constipation, particularly in children with PFD or dyssynergic defecation.

Autoimmune pancreatitis type 2 (idiopathic duct-centric pancreatitis): A comprehensive review.

Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.

The case fatality rate of COVID-19 during the Delta and the Omicron epidemic phase: A meta-analysis.

As coronavirus variants are constantly occurring, we tried to understand more about the omicron and delta variants that have hit the world. We provided dynamic information on the case fatality rate (CFR) of the Omicron variant over time and to compare it with that of the Delta variant through meta-analysis. Twenty-four countries were selected by submission counts, submission dates, and confirmed cases. We defined the Delta or the Omicron epidemic period for individual countries as when each variant is over 90%. We further analyzed the Omicron period by dividing it into the initial plateau, increasing, and decreasing phases according to the number of newly confirmed daily cases. Finally, the meta-analysis examined the summary and between-study heterogeneity. The CFR of COVID-19 during the Omicron epidemic was lower than that during the Delta epidemic (odds ratio [OR]: 0.252, 95% confidence interval [CI] 0.205-0.309). The CFR of COVID-19 during the initial plateau phase of Omicron was higher than during other phases. (OR: 1.962, 95% CI 1.607-2.397). The CFR of COVID-19 during the increasing phase was lower than during the decreasing phases (OR: 0.412, 95% CI 0.342-0.498). The Omicron variant had lower CFR compared to the Delta variant, and the initial plateau phase had higher CFR compared to the noninitial phases. These results can help establish global health policies for COVID-19 in the future.

The impact of urinary incontinence on multiple health outcomes: an umbrella review of meta-analysis of observational studies.

BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.

Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.

Current status of premature mortality from four non-communicable diseases and progress towards the Sustainable Development Goal target 3.4: a population-based study in northeast China, 2004-2017.

BACKGROUND AND AIM: According to the United Nations' Sustainable Development Goal (SDG) target 3.4, premature mortality from four non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes mellitus, collectively referred to as NCD4) should achieve a minimum decline of 33% in 2030 relative to 2015. This remains a challenge for China. This study aimed to evaluate the current status and progress towards this target in Liaoning Province, one of the three provinces in northeast China. METHODS: We calculated the premature mortality rates (PMRs) per year and average annual percentage changes (AAPCs) from NCD4 using mortality data between 2004 and 2017. The trend was analyzed in the whole population, as well as in subpopulations of gender (male/female) and inhabiting area (urban/rural). PMRs from NCD4 for 2030 were projected by fitting a linear regression based on the current trend, which was identified by a Joinpoint model. FINDINGS: In the whole population, only chronic respiratory diseases showed a significant decline (AAPC: - 6.5%, p < 0.05), while only cancer showed a significant increase (AAPC: + 1.3%, p < 0.05); taken together, NCD4 showed a significant increase (AAPC: + 0.6%, p < 0.05). In the subpopulations, while males showed a significant increase in NCD4 (AAPC: + 1.5%, p < 0.05), cardiovascular diseases (AAPC: + 1.7%, p < 0.05), cancer (AAPC: + 1.8%, p < 0.05), and diabetes mellitus (AAPC: + 4.2%, p < 0.05), females showed a significant decline in NCD4 (AAPC: - 1.2%, p < 0.05), cardiovascular diseases (AAPC: - 1.8%, p < 0.05), diabetes mellitus (AAPC: - 2.1%, p < 0.05), but showed a mild increase in cancer (AAPC: + 0.5%, p > 0.05). A comparative analysis of the projected PMRs for 2030 with the 2015 levels revealed that only chronic respiratory diseases are expected to achieve the SDG target 3.4, apart from in the urban male subpopulation. CONCLUSION: Except for chronic respiratory diseases, NCD4 cannot be expected to achieve the SDG target 3.4 in the whole population of Liaoning Province. Under these circumstances, special attention should be paid to reducing the risks of cancer and providing preventative interventions for men.

Anatomical study of the left colic artery in laparoscopic-assisted colorectal surgery.

BACKGROUND: It is important for lymph node dissection around the inferior mesenteric artery (IMA) with preservation of the left colic artery (LCA) to be aware of the track and the length of the LCA. We aimed to investigate the branching pattern and trajectory of LCA and measure the distances from the root of the IMA to the origin of the LCA (D mm) and from the origin of LCA to intersection of LCA and IMV (d mm) during laparoscopic left-sided colorectal operations. METHODS: We analyzed 106 patients who underwent laparoscope-assisted left-side colorectal surgery during laparoscopic surgery. The branching patterns among the IMA, LCA, and sigmoidal trunk were evaluated; the trajectory of LCA was examined; the D mm and d mm were measured using a length of silk in the surgical operation. RESULTS: In 59.5% patients, the LCA arose independently from the sigmoidal trunk (type A); in 8.5% patients, the LCA and sigmoidal trunk arose from the IMA at the same point (type B); in 29.2% patients, the LCA and sigmoidal trunk had a common trunk (type C); the LCA did not exist in 2.8% (type D).The D mm and d mm for all cases ranged from 15.0 to 65.3 mm (median, 43.1 mm) and from 20.3 to 46.2 mm (median, 34.8 mm), respectively. 74.8% of the LCA went straight upper left and upward to proximal part of descending colon (type I), 25.2% went to the lower left at first, then turned to travel straight upward to proximal part of descending colon (type II). CONCLUSION: This study showed the anatomic variations of LCA during laparoscopic left-sided colorectal operation, which would help surgeons safely perform laparoscopic surgery in the left-side colon and rectum.

Effect of exosomal miRNA on cancer biology and clinical applications.

Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.

Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment.

Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.

The Biological Effect and Clinical Application of Long Noncoding RNAs in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the world. Easier recurrence and metastasis is the main cause of mortality in CRC patients, and the markers applied for diagnosis and treatment of CRC is still urgently needed to early diagnose and evaluate therapeutic effect. Long noncoding RNA (lncRNA) is a class of noncoding RNA that the length is more than 200 nucleotides. With the development of sequencing technique about transcriptome, increasing lncRNAs are focused on their function and mechanism related to the nosogenesis and pathology of CRC. Recent studies report that lncRNAs acted as crucial role in CRC and could be as biomarker for CRC diagnosis and treatment. In this review, we display the regulation of lncRNA by interacting with DNA, RNA and protein and highlight the double role of lncRNAs as oncogene or anti-tumor gene involved in Wnt signaling pathway, p53 signaling pathway or others to be an regulator in CRC development. Lastly, we discuss some new finding of lncRNAs, especially lncRNA in exosome, which could be as potential markers for diagnosis and treatment of CRC in future.

LncRna CPS1-IT1 Suppresses Cell Proliferation, Invasion and Metastasis in Colorectal Cancer.

BACKGROUND/AIMS: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. METHODS: Expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. RESULTS: Expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. CONCLUSION: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.

Computed tomography scan is superior to x-ray plain film in the diagnosis of gastrointestinal tract perforation.

Gastrointestinal (GI) tract perforation is one of the most severe acute abdomens. In clinical practice, abdominal x-ray plain film remains the first-line diagnostic modality for this entity. A proportion of the perforated patients, however, do not exhibit a classic x ray sign: free air at the subphrenic area. This insufficiency can bring difficulties to the diagnosis, delay appropriate treatments, and even cause lethal consequences. We describe herein a case of GI tract perforation, which was not detected by the abdominal x-ray plain film initially. Strikingly, the abdominal computed tomographic (CT)scan established the diagnosis and predicted the site and cause of the perforation, which were consistent with the intraoperative findings and pathological examination. In addition, CT scan was useful in monitoring the progression of the disease. Given the high performance of CT scan in the present case, we recommend it as a preferred diagnostic modality for patients who are suspected of GI perforation,especially when the abdominal x-ray plain film is inconclusive.

Long-term prognosis of surgical treatment for early ampullary cancers and implications for local ampullectomy.

BACKGROUND: Early ampullary cancers present with good prognosis. Pancreaticoduodenectomy (PD) has been standard treatment for ampullary cancers, but it remains high rate of postoperative complications. So there raises a discussion on the role of local ampullectomy for early ampullary cancers (mainly focusing on pT1). METHODS: 89 patients with pT1 ampullary cancer who underwent surgical treatment between 1978 and 2010 were retrospectively studied. RESULTS: Rate of postoperative complications, especially post-operative pancreatic fistula (P = 0.009), after PD was higher than after local ampullectomy, . Multivariate analysis showed that tumor size (HR 2.204; P = 0.014), lymph node metastasis (HR 4.362; P < 0.001), lymph vascular invasion (HR 4.258; P < 0.001), and perineural invasion (HR 4.467; P < 0.001), gross morphology (HR 2.536; P = 0.004) and tumor grade (HR 4.213; P = 0.001) were independent risk factors for long-term survival, as well as risk factors for failure of ampullectomy in early ampullary cancer. For patients absent of these factors, local ampullectomy would achieve a good prognosis. CONCLUSIONS: Because of high rate of lymph node metastasis, PD should be preferably performed for radical resection. Local ampullectomy could be an alternative for patients in high operative risk; and would achieve a good outcome in patients whose tumors were well differentiated and showed polypoid gross morphology and size ≤1 cm.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al. The authors identified higher serum immunoglobulin (Ig) G4 levels and age over 55 years as independent risk factors for disease relapse. Despite notable strengths, it is crucial to address potential biases. Firstly, the cohort study included 189 patients with autoimmune pancreatitis (AIP) type 1 (with higher IgG4 seropositivity and higher relapse) and 24 with type 2 (with lower IgG4 seropositivity and lower relapse). Consequently, most, if not all, AIP type 2 patients were assigned to the normal group, possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse. Secondly, the authors did not provide sufficient details regarding AIP diagnosis, such as the ratio of definitive vs probable cases and the proportion of biopsies. In cases where histological evidence is unavailable or indeterminate, AIP type 2 may be misdiagnosed as definitive type 1, and type 1 may also be misdiagnosed as probable type 2, particularly in cases with normal or mildly elevated serum IgG4 levels. Lastly, in this retrospective study, approximately one-third of the consecutive patients initially collected were excluded for various reasons. Accordingly, the impact of non-random exclusion on relapse outcomes should be carefully considered. In conclusion, the paper by Zhou et al offers plausible, though not entirely compelling, evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse. The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping, heavily dependent on obtaining histological specimens. In this regard, endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process, contributing to mitigating biases in future explorations of the disease.

An integrated city-driven perinatal HIV prevention program covering 1.8 million pregnant women in Shenzhen, China, 2000 to 2010.

BACKGROUND: Despite the scale-up of prevention of mother-to-child transmission (PMTCT) programs worldwide, the translation from research studies into public health policy has been slow. This report details the experiences of a city-driven PMTCT program in China using existing health resources. METHODS: The PMTCT program was devised to hospital based and city-wide. It achieves full use of available resources: the local Centers for Disease Control and Prevention, the Infectious Disease Hospital, Maternal and Child Health Hospitals, and all qualified comprehensive hospitals. RESULTS: From 2000 to 2010, 1,843,122 pregnant women attended prenatal care or labor and delivery services. Overall, 97.4% received pretest HIV counseling, and 96.2% were tested for HIV. Among the 81.1% (1,495,122) of women who attended prenatal clinics, 97.2% (1,452,753) received pretest counseling and 95.7% (1,430,799) were tested for HIV. Among the 18.9% (348,000) of women with an undocumented HIV status at labor and delivery, 98.6% (343,038) received pretest counseling, and 98.1% (341,371) were tested for HIV. In total, 229 women were determined HIV positive for a prevalence of 1.3 per 10,000 pregnant women. Among the 107 HIV-infected women who carried to delivery, 87.9% received antiretroviral prophylaxis for themselves and their infants. Among the 58 women who were identified HIV positive at labor, 10.3% of mothers and 72.4% of infants received antiretroviral prophylaxis. The estimated mother-to-child transmission rate was 5.3% (95% confidence interval, 2.2%-10.7%). CONCLUSIONS: With appropriate integration, existing health care resources are adequate for a comprehensive city-driven PMTCT program in an area with a low HIV prevalence.

Perceived discrimination, social support, and perceived stress among people living with HIV/AIDS in China.

Perceived stress among people living with HIV/AIDS (PLWH) was associated with severe mental health problems and risk behaviors. Discrimination toward PLWH in China is prevalent. Both perceived discrimination and social supports are determinants of the stress level among PLWH. Psychological support services for PLWH in China are scarce. It is unknown whether social support is a buffer between the perceived discrimination and perceived stress. With written consent, this study surveyed 258 PLWH recruited from multiple sources in two cities in China. Instruments were validated in previous or the present study, including the perceived stress scale for PLWH (PSSHIV), the perceived social support scale (PSSS), and the perceived discrimination scale for PLWH (PDSHIV). Pearson correlations and multiple regression models were fit. PDSHIV was associated with the Overall Scale and all subscales of PSSHIV, whilst lower socioeconomic status in general and lower scores of PSSS were associated with various subscales of PSSHIV. The interaction item (PSSS×PSDHIV) was nonsignificant in modeling PSSHIV, hence no significant moderating effect was detected. Whilst perceived discrimination is a major source of stress and social support can reduce stress among PLWH in China, improved social support cannot buffer the stressful consequences due to perceived discrimination. The results highlight the importance to reduce discrimination toward PLWH and the difficulty to alleviate its negative consequences. It is warranted to improve mental health among PLWH in China and it is still important to foster social support among PLWH as it has direct effects on perceived stress.

Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-κB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue.

Apurinic/apyrimidinic endonuclease-1 (APE-1), a key enzyme responsible for DNA base excision repair (BER), has been linked to cancer chemoradiosensitivity. The phosphorylation of p65 plays a role in the activation of this pathway. In this study, we investigated APE-1 expression and its interaction with p65 in esophageal squamous cell carcinoma (ESCC) tissue. The expression of APE-1, p65, p65 nuclear localization sequence (p65-NLS), and monocyte chemoattractant protein-1 (MCP-1) was assessed by immunohistochemical analysis in 67 human ESCC tissue samples. Real-time PCR and western blotting were also performed. p65 siRNA was evaluated to determine the role of p65 in the regulation of APE-1 expression. We found nuclear localization of APE-1 in 89.6% (60/67) of ESCC tissue samples. We also observed the colocalization of p65-NLS and APE-1 in esophageal cancer tissue. In KYSE220 cells, pretreatment of MG-132 significantly abrogated upregulation of p65 and APE-1 levels induced by MCP-1, and treatment with 10 and 20 nM p65 siRNA significantly inhibited APE-1 mRNA expression. siRNA for p65 treatment significantly increased the apoptotic index in 5-FU-treated KYSE220 cells. We conclude that APE-1 is overexpressed and mainly localized in the nuclear compartment of cancer cells, and partly regulated by p65 in the NF-κB pathway in ESCC tissue.

Posterior reversible encephalopathy syndrome and autoimmunity.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome characterized by acute or subacute onset of neurological symptoms (e.g., headache, seizure, confusion, vomiting, and diminished eyesight) and impaired endothelial barrier function of the cerebral circulation that leads to bilateral subcortical vasogenic edema, while exhibiting a "reversible" feature in most cases. Clinically, various predisposing or precipitating conditions have been identified, such as hypertension, autoimmune diseases, renal dysfunction/failure, preeclampsia/eclampsia, post-transplantation conditions, and certain therapeutic agents. Among several putative mechanisms, the immune activation hypothesis prevails, as up to 50% of patients with PRES harbor abnormalities related to autoimmunity, such as concurrent systemic lupus erythematosus. In this Review, we summarize the clinical and laboratory evidence that places PRES in the context of autoimmunity.

Twelve years after the ARRIVE guidelines: Animal research has not yet arrived at high standards.

The reproducibility crisis across animal studies jeopardizes the credibility of the main findings derived from animal research, even though these findings are critical for informing human studies. To clarify and improve transparency among animal studies, the ARRIVE reporting guidelines were first announced in 2010 and upgraded to version 2.0 in 2020. However, compliance with and awareness of those reporting guidelines has remained suboptimal. Journal editors should encourage the authors to adhere to those guidelines. Authors, editors, referees, and reviewers should be aware of the ARRIVE guideline 2.0 when assessing and evaluating the methodology and findings of animal studies. However, we should also question whether reporting guidelines alone can change a research culture and improve the reproducibility of animal investigations. Reported research may not reflect actual research. Large segments of animal research efforts are wasted because of poor design choices and because of non-publication rather than suboptimal reporting. Better training of the scientific workforce, interventions at improving animal research at the design stage, registration practices, and alignment of the reward system with the publication of rigorous animal research may achieve more than reporting guidelines alone.