Analysis of endoscopic and pathological features of 6961 cases of gastric cancer.

Gastric cancer (GC) stage and tissue differentiation affect treatment efficacy and prognosis, highlighting the importance of understanding the risk factors that affect these parameters. Therefore, this study analyzed risk factors affecting the GC stage and differentiation and the relationships between the cancer site and the sex and age of the patient. We collected clinical data from 6961 patients with GC, including sex, age, endoscopic lesion location, and pathological differentiation. Patients were grouped based on GC stage (early or advanced), differentiation (well or poorly differentiated), and lesion site (upper stomach [cardia and fundus], middle stomach [gastric body], and lower stomach [gastric antrum]). Differences in sex, age, location, stage, and degree of differentiation were assessed based on these groupings. Univariate analysis revealed that the disease location and differentiation significantly differed based on the GC stage (P < 0.05), whereas sex, age, site, and stage significantly differed based on GC differentiation (P < 0.05). A multivariate analysis confirmed these factors as independent risk factors affecting GC. Moreover, lesion sites significantly differed between sexes (P < 0.05) and among age groups (P < 0.05). Although the effects of family history, lifestyle, and Helicobacter pylori infection status of the patients were not considered, this single-center retrospective study established independent risk factors for GC.Trial registration ChiCTR2200061989.

Prognostic significance of high NPC2 expression in gastric cancer.

Gastric cancer is one of the most common malignancies worldwide, and the third leading cause of cancer-related death. The identification of novel biomarkers and therapeutic targets is critical to improve the prognosis. A total of 380 patients with primary gastric cancer from the TCGA database were analyzed. The receiver operating characteristic curves were plotted. We further evaluated the independent prognostic ability of NPC2 expression for overall survival (OS) and relapse-free survival (RFS) through the Kaplan-Meier curve and Cox analysis. The NPC2 expression was significantly higher (P < 0.001) in gastric cancer. High NPC2 expression was significantly (P < 0.0001) associated with poor OS and poor RFS. The age, stage, radiation therapy, residual tumor, and NPC2 expression showed independent prognostic value for OS. The gender and NPC2 expression showed independent prognostic value for RFS. The higher NPC2 expression was observed in gastric cancer, compared with adjacent normal tissue (P < 0.001), confirmed by the IHC staining. The CCK-8 assay showed that NPC2 knockdown inhibits cell proliferation while NPC2 overexpression promotes cell proliferation (P < 0.05). NPC2 expression may serve as a promising prognostic biomarker for patients with gastric cancer.

Transition Metal Dichalcogenides Nanoscrolls: Preparation and Applications.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) nanosheets have shown extensive applications due to their excellent physical and chemical properties. However, the low light absorption efficiency limits their application in optoelectronics. By rolling up 2D TMDCs nanosheets, the one-dimensional (1D) TMDCs nanoscrolls are formed with spiral tubular structure, tunable interlayer spacing, and opening ends. Due to the increased thickness of the scroll structure, the light absorption is enhanced. Meanwhile, the rapid electron transportation is confined along the 1D structure. Therefore, the TMDCs nanoscrolls show improved optoelectronic performance compared to 2D nanosheets. In addition, the high specific surface area and active edge site from the bending strain of the basal plane make them promising materials for catalytic reaction. Thus, the TMDCs nanoscrolls have attracted intensive attention in recent years. In this review, the structure of TMDCs nanoscrolls is first demonstrated and followed by various preparation methods of the TMDCs nanoscrolls. Afterwards, the applications of TMDCs nanoscrolls in the fields of photodetection, hydrogen evolution reaction, and gas sensing are discussed.

Donor hepatic artery reconstruction based on human embryology: A case report.

BACKGROUND: Embryonic hepatic artery anatomy simplifies its identification during liver transplantation. Injuries to the donor hepatic artery can cause complications in this process. The hepatic artery's complex anatomy in adults makes this step challenging; however, during embryonic development, the artery and its branches have a simpler relationship. By restoring the embryonic hepatic artery anatomy, surgeons can reduce the risk of damage and increase the procedure's success rate. This approach can lead to improved patient outcomes and lower complication rates. CASE SUMMARY: In this study, we report a case of donor liver preparation using a donor hepatic artery preparation based on human embryology. During the preparation of the hepatic artery, we restored the anatomy of the celiac trunk, superior mesenteric artery, and their branches to the state of the embryo at 5 wk. This allowed us to dissect the variant hepatic artery from the superior mesenteric artery and left gastric artery during the operation. After implanting the donor liver into the recipient, we observed normal blood flow in the donor hepatic artery, main hepatic artery, and variant hepatic artery, without any leakage. CONCLUSION: Donor hepatic artery preparation based on human embryology can help reduce the incidence of donor hepatic artery injuries during liver transplantation.

Effect of adipose tissue-derived stem cells therapy on clinical response in patients with primary Sjogren's syndrome.

The purpose of this trial was to clinically assess the effect and safety of Adipose Tissue-derived Stem Cells (ADSCs) treatment on primary Sjogren's Syndrome (pSS). In this 6-month randomized, triple-blind, placebo-controlled clinical trial, pSS patients were randomly assigned to two groups. After demographic characteristics and clinical examination were achieved, local injection of ADSCs into bilateral glands was performed with patients in ADSCs group (n = 35) and placebo solution was used for another group (n = 39) at three time points. Patients were followed up at 1-, 3- and 6-month. At each visit, studies of clinical and laboratory outcomes, as well as subjective symptoms, were conducted. A total of 74 subjects who met the including criteria were allocated in two groups and eventually 64 subjects (86.5%) completed the treatments and the follow-up assessments. Secretion of salivary and lachrymal glands were significantly improved in 3-month (P < 0.05). A great improvement of European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) was found after ADSCs treatment with intergroup comparison from baseline to follow-up (P < 0.05). There is also a significant difference of European Alliance of Associations for Rheumatology SS Patient Reported Index (ESSPRI) between the two groups in the follow-up (P < 0.05). A significant abatement of IgG, IgM, C3, C4 and ESR between two groups was observed in part of follow-up time points (P < 0.05). The ADSCs therapy can provide relief of oral and eye's dryness in our trial in a short time and has potential improvement of subjective and systemic syndromes of pSS.

Predicting reflux symptom recurrence: The impact of gastroesophageal junction indicators and body mass index among outpatients.

The present study aimed to evaluate the efficacy of the prediction model in predicting reflux symptom recurrence among outpatients with reflux esophagitis (RE). A total of 261 outpatients diagnosed with RE complicated by anatomical alterations at the gastroesophageal junction and reflux symptoms were included in the study. Through follow-up, patients were divided into a General group (149 cases) and a Recurrent group (112 cases). Receiver operating characteristic curves of the related factors and prediction model were analyzed to compare the efficacy of each element in predicting reflux recurrence. A prediction model was constructed for predicting reflux recurrence using the axial length of the hiatal hernia (HH), the diameter of the esophageal hiatus, Hill classification, and body mass index (BMI) as risk factors. The cutoff values of the aforementioned factors for predicting reflux recurrence were: an axial length of HH >2 cm, esophageal hiatus diameter ≥3 cm, Hill grade >III, and BMI >25.1 kg/m2. The multivariate prediction model constructed using the aforementioned four indicators together with chronic atrophic gastritis and Helicobacter pylori infection had the area under the curve of 0.801 (95% confidence interval: 0.748-0.854), and the cutoff value of 46.8 had a sensitivity and specificity of 71.4% and 75.8%, respectively. The predictive model in the present study can be used for the primary assessment of reflux recurrence in patients with RE.

Evaluation of the detection rate of high­grade gastric intraepithelial neoplasia using linked color imaging and white light imaging.

As an endoscopic technology for the enhancement of images, linked color imaging (LCI) performs well when used for the early detection and diagnosis of gastrointestinal cancer. However, literature data are lacking for LCI in the detection of high-grade gastric intraepithelial neoplasia. Therefore, the aim of the present study was to investigate the efficacy of LCI compared with traditional white light imaging (WLI) in the detection of high-grade gastric intraepithelial neoplasia via the comparison of detection rates between senior and junior endoscopists using both techniques. Overall, 84 lesions from 81 patients with high-grade gastric intraepithelial neoplasia diagnosed between January 2017 and December 2017 were considered. Following the exclusion of three patients with two lesions, 78 patients who had only one lesion were enrolled. The two types of endoscopy, WLI and LCI, were performed in the same patients under the same conditions. Four senior and four junior endoscopists retrospectively compared the images. The detection rate of high-grade gastric intraepithelial neoplasia was significantly higher with LCI than with WLI when performed by senior and junior endoscopists. With WLI, the detection rate obtained by senior endoscopists was significantly higher than that obtained by junior endoscopists. However, for LCI, the detection rates for junior and senior endoscopists were comparable. Interobserver agreement was good to satisfactory. These findings indicate that LCI is superior to WLI in the detection and identification of gastric cancer and provides highly accurate diagnostic results from endoscopic examinations, regardless of the experience of the endoscopist. LCI may be used to narrow the gap in the detection rate of high-grade gastric intraepithelial neoplasia between junior and senior endoscopists.

De Novo Assembly and Characterization of the Transcriptome of an Omnivorous Camel Cricket (Tachycines meditationis).

Tachycines meditationis (Orthoptera: Rhaphidophoridae: Tachycines) is a widely distributed insect in eastern Asia. This species is common in urban environments, and its unique omnivorous diet may contribute to its success in various habitats. However, molecular studies on the species are scarce. Here, we obtained the first transcriptome sequence of T. meditationis and performed preliminary analyses to test whether the evolution of coding sequences fits the expectations based on the species' ecology. We retrieved 476,495 effective transcripts and annotated 46,593 coding sequences (CDS). We analysed the codon usage and found that directional mutation pressure was the leading cause of codon usage bias in this species. This genome-wide relaxed codon usage pattern in T. meditationis is surprising, given the potentially large population size of this species. Moreover, despite the omnivorous diet, the chemosensory genes of this species do not exhibit codon usage deviating significantly from the genome-level pattern. They also do not seem to experience more gene family expansion than other cave cricket species do. A thorough search for rapidly evolved genes using the dN/dS value showed that genes associated with substance synthesis and metabolic pathways, such as retinol metabolism, aminoacyl-tRNA biosynthesis, and fatty acid metabolism, underwent species-specific positive selection. While some results seem to contradict the species ecology, our transcriptome assembly provides a valuable molecular resource for future studies on camel cricket evolution and molecular genetics for feeding ecology in insects, in general.

Comparison of missed adenomas in deep-sedated and unsedated colonoscopy: A multicenter retrospective study.

BACKGROUND: Deep-sedated colonoscopy with propofol is widely used in China. However, its impact on quality metrics remains controversial. We aimed to investigate the effects of deep-sedated colonoscopy on missed adenomas, specifically in each colorectal segment. METHODS: Data of 3710 individuals from seven hospitals in China who underwent an initial colonoscopy with or without propofol sedation and a second colonoscopy without sedation within six months for surveillance or polypectomy by endoscopist of the same level between October 2020 and September 2021 were retrospectively analyzed. RESULTS: A total of 1113 missed adenomas in 3710 patients were evaluated. The adenoma miss rate (AMR) was significantly higher in deep-sedated colonoscopy than in unsedated colonoscop [19.14% (578/3020) vs. 16.15% (535/3313), P < 0.05]. The risk of missing adenomas in deep-sedated colonoscopy was 1.229 times higher than in unsedated colonoscopy (OR, 1.229; 95% CI: 1.080-1.399). AMRs of the splenic flexure (26.02% [96/369] vs. 16.04% [47/293], P < 0.05) and descending colon (20.86% [102/489] vs. 13.37% [54/404], P < 0.05) were significantly higher in deep-sedated colonoscopy than in unsedated colonoscopy when performed by middle-level endoscopists rather than high-level endoscopists (P < 0.05). CONCLUSIONS: AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy. Furthermore, adenomas in the splenic flexure and descending colon were more frequently missed in deep-sedated colonoscopy than in unsedated colonoscopy, particularly when performed by less experienced endoscopists.

Comparison of adenoma detection in different colorectal segments between deep-sedated and unsedated colonoscopy.

To investigate if deep-sedated colonoscopy affects adenoma detection in certain colorectal segment. Review of colonoscopy reports, electronic images and medical records of individuals underwent screening colonoscopy with or without propofol sedation between October 2020 and March 2021 from seven hospitals in China. A total of 4500 individuals were analyzed. There was no significant difference in ADR between deep-sedated colonoscopy and unsedated colonoscopy [45.4% vs. 46.3%, P > 0.05]. The APP of deep-sedated colonoscopy was lower than unsedated colonoscopy (1.76 ± 0.81 vs. 2.00 ± 1.30, P < 0.05). Both average number of adenomas and luminal distention score of splenic flexure and descending colon were lower in deep-sedated colonoscopy (P < 0.05), and average number of adenomas was positively correlated with an improved distension score in splenic flexure and descending colon (splenic flexure r = 0.031, P < 0.05; descending colon r = 0.312, P < 0.05). Linear regression model showed deep-sedated colonoscopy significantly affected luminal distention of splenic flexure and descending colon as well as average number of adenomas detected in splenic flexure (P < 0.05). Deep-sedated colonoscopy decreased adenoma detection in splenic flexure and the luminal distention of splenic flexure and descending colon compared with unsedated colonoscopy.

Comparison of three sedation models for same-day painless bidirectional endoscopy: A multicenter randomized controlled trial.

BACKGROUND AND AIM: We investigated the most beneficial propofol sedation model for same-day painless bidirectional endoscopy (BDE). METHODS: Asymptomatic participants scheduled for same-day painless BDE examination from October 2020 to September 2021 were randomized to three groups: sedated esophagogastroduodenoscopy followed by unsedated colonoscopy (Group A); sedated esophagogastroduodenoscopy followed by sedated colonoscopy (Group B); and sedated esophagogastroduodenoscopy followed by sedated insertion colonoscopy (Group C). Patient discomfort, colonoscopy performance, doses of propofol, cardiovascular stress, anesthesia resuscitation, and sedation-related adverse events were evaluated. RESULTS: A total of 3200 participants were analyzed. Baseline demographics, patient discomfort, cecal intubation rate, adenoma detection rate and sedation-related adverse events were similar in the three groups. Propofol dose was the lowest in Group A (137.65 ± 36.865 mg) compared with Group B (177.71 ± 40.112 mg, P < 0.05) and Group C (161.63 ± 31.789 mg, P < 0.05). Decline in vital signs was most obvious in Group B during the procedure (P < 0.05). Recovery time was the shortest in Group A (5.01 ± 1.404 min) compared with Group B (9.51 ± 2.870 min, P < 0.05) and Group C (5.83 ± 2.594 min, P < 0.05); discharge time was the shortest in Group A (3.53 ± 1.685 min) compared with Group B (11.29 ± 5.172 min, P < 0.05) and Group C (6.47 ± 2.338 min, P < 0.05). Adenomas per positive patient of Group A (2.29 ± 1.055) and Group C (2.28 ± 0.931) were more than that in Group B (2.11 ± 0.946, P < 0.05). CONCLUSIONS: Sedated esophagogastroduodenoscopy followed by unsedated colonoscopy is the superior model for same-day painless BDE with the benefits of satisfactory patient comfort, reduced sedation dose, less cardiovascular stress, faster recovery, shorter discharge time and high colonoscopy quality.

Predicting Rate Constants of Hydroxyl Radical Reactions with Alkanes Using Machine Learning.

The hydrogen abstraction reactions of the hydroxyl radical with alkanes play an important role in combustion chemistry and atmospheric chemistry. However, site-specific reaction constants are difficult to obtain experimentally and theoretically. Recently, machine learning has proved its ability to predict chemical properties. In this work, a machine learning approach is developed to predict the temperature-dependent site-specific rate constants of the title reactions. Multilayered neural network (NN) models are developed by training the site-specific rate constants of 11 reactions, and several schemes are designed to improve the prediction accuracy. The results show that the proposed NN models are robust in predicting the site-specific and overall rate constants.

Results of endoscopy in 35,525 patients with precancerous diseases of the gastrointestinal tract.

BACKGROUND: To explore the need for the high-risk and general population to undergo endoscopy and the best age for these two groups to do so. MATERIAL AND METHODS: Data on 35,525 patients who underwent endoscopy in the Endoscopic Center of Shanxi Cancer Hospital and associated medical group hospitals from January 2016 to December 2019 were collected. Two aspects of the high-risk and general population were analyzed retrospectively: 1. The detection rate of precancerous diseases. 2. The difference and distribution of the detection rate in different genders, different ages, and different pathologic types. RESULTS: A total of 35,525 patients, 24,185 in the general population and 11,340 in the high-risk population, were examined by electronic gastroscopy and colonoscopy simultaneously. Of these, 20,659 were men and 14,866 were women. The detection rate of gastric diseases (gastric cancer, gastric polyp, gastric ulcer, chronic atrophic gastritis) in the general population was 9.27%, and that in the high-risk population was 25.18%. The detection rate of colonic polyps was 53.76% in the general population and 56.77% in the high-risk population. CONCLUSION: Both the high-risk and the general population should consider gastroscopy and colonoscopy as routine physical examination items. Routine gastroscopy is highly recommended for the high-risk population. The general population should pay close attention to their colonoscopy results. The best screening age for both populations is 40 years old and above.

The value of serum Krebs von den lungen-6 as a diagnostic marker in connective tissue disease associated with interstitial lung disease.

OBJECTIVES: The purpose of this study was to evaluate the value of serum krebs von den lungen-6 (KL-6) level as a diagnostic indicator for connective tissue disease associated with interstitial lung disease (CTD-ILD). METHODS: One hundred fifty five patients with newly diagnosed CTD in our hospital were enrolled and divided into two groups by their ILD manifestations, the CTD-ILD group and the CTD group. In parallel, 61 patients with pulmonary infection and 60 cases of healthy subjects were also enrolled into the study. The difference of serum KL-6 level among the four groups were compared. In CTD-ILD group, carbon monoxide diffusing capacity (DLCo) and high-resolution computed tomography (HRCT) of lung were also tested. The serum KL-6 level of 32 patients from the CTD-ILD group who received cyclophosphamide (CTX) pulse therapy were sampled and measured, by enzyme linked immunosorbent assay (ELISA), at three time points: before treatment, 3 months after treatment and 6 months after treatment. RESULTS: The serum KL-6 level in the CTD-ILD group (1004.9 (676.41738.1) IU/ml) is significantly higher than three other groups (χ2 = 72.29, P < 0.001). In the CTD-ILD group the level of serum KL-6 was positively correlated with disease severity on HRCT (r = 0.75, P <  0.001), while was negatively correlated with DLCo (r = - 0.50, P <  0.001). In 32 patients who received CTX pulse therapy, the level of serum KL-6 was gradually decreased in 20 cases whose lesions were absorbed within 6 months (F = 13.67, P <  0.001), whereas it remained unchanged in the rest of 12 patients (Z = -1.328, P = 0.198). CONCLUSIONS: Serum KL-6 level can potentially serve as a diagnostic marker for CTD-ILD and be utilized to evaluate the effectiveness of CTX pulse therapy.

Effect of ANGPTL7 on Proliferation and Differentiation of MC3T3-E1 Cells.

BACKGROUND Angiopoietin-like proteins (ANGPTL) are a family of secretory glycoproteins that are involved in many pathophysiological processes. ANGPTL7 is a newly-discovered member of the ANGPTL family and plays a role in corneal morphogenesis, angiogenesis, glaucoma, and cancer. To date, whether ANGPTL7 is involved in osteoporosis is unknown. Therefore, to discover the effects of ANGPTL7 on osteoporosis, we explored the expression of ANGPTL7 in preosteoblasts and assessed the mechanism underlying its effects on proliferation and differentiation abilities of preosteoblasts. MATERIAL AND METHODS Mouse MC3T3-E1 cells were cultured in osteogenic medium for osteogenic differentiation. The expression levels of ANGPTL7 were detected by RT-qPCR and Western blot assays. Moreover, the overexpressed plasmid of ANGPTL7 pMSCV-ANGPTL7 was transfected into MC3T3-E1 cells. CCK-8 was used to evaluate cell proliferation. ALP activity detection and alizarin red staining were performed to measure the effect of ANGPTL7 on osteogenic differentiation. The expression levels bone morphogenetic proteins (BMPs) and osteogenic markers ALP, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen I (Col I) were analyzed by Western blot. RESULTS When MC3T3-E1 cells were exposed to osteogenic medium, there was a significant increase in ANGPTL7, and overexpression of ANGPTL7 markedly promoted cell proliferation, ALP activity, and mineralization. Moreover, ANGPTL7 upregulated the levels of BMPs, especially BMP2/7, and the osteogenic markers ALP, Runx2, OCN, and Col I. CONCLUSIONS The results suggest that by regulating the expression of BMPs, ANGPTL7 directly promotes proliferation, differentiation, and mineralization of osteoblasts.

HOTAIR promotes osteosarcoma development by sponging miR-217 and targeting ZEB1.

Long noncoding RNAs (lncRNAs) have drawn increasing attention because of the role which they play in various diseases, including osteosarcoma. So far, the function and mechanism of HOTAIR in osteosarcoma are unclear. In our study, we observed that HOTAIR was elevated accompanied with a decrease of miR-217 and an increase of ZEB1 in human osteosarcoma cells including U2OS, MG63, Saos-2, and SW1353 compared with human osteoblast cell line hFOB. In addition, the subsequent functional assay exhibited that silencing HOTAIR could significantly repress osteosarcoma cell growth, migration, invasion, and induce cell apoptosis capacity, which indicated that HOTAIR exerted an oncogenic role in osteosarcoma. Moreover, it was revealed by using bioinformatics analysis that HOTAIR can be targeted by microRNA-217 (miR-217). miR-217 has been recognized as a crucial tumor suppressive gene in cancers. We verified that mimics of miR-217 were able to suppress the osteosarcoma development. Furthermore, real-time quantitative PCR showed that HOTAIR siRNA increased miR-217 expression. Besides these, ZEB1 was identified as a downstream gene of miR-217 and we found that HOTAIR can mediate osteosarcoma progress by upregulating ZEB1 expression via acting as a competitive endogenous RNA (ceRNA) via miR-217. Taken these together, our findings in this study indicated that HOTAIR/miR-217/ZEB1 axis, as a novel research point can provide new insights into molecular mechanism of osteosarcoma development.

Polysaccharides from Dendrobium officinale inhibit bleomycin-induced pulmonary fibrosis via the TGFß1-Smad2/3 axis.

Polysaccharides from Dendrobium officinale (PDO) have been found to elicit significant benefits for patients with fibrotic diseases. However, there are no reports on treatment of idiopathic pulmonary fibrosis (IPF) using PDO. The aim of this paper was to investigate the therapeutic effects of PDO on IPF and its underlying mechanisms. Our data showed that PDO significantly ameliorated indices for both pulmonary inflammation and fibrosis in a bleomycin (BLM)-induced pulmonary fibrosis model in rats, which was associated with inactivation of transforming growth factor ß1 (TGFß1)-Smad2/3 signaling pathway. Moreover, PDO effectively blocked TGFß1-induced transformation of rat alveolar epithelial type II cells into myofibroblasts, with the inhibition of total Smad2/3, pSmad2/3, collagen I and fibronectin protein expression in a dose-dependent manner in vitro. Therefore, PDO may represent as a promising candidate biomacromolecule drug for the safe and effective therapy of IPF.

Microsurgical anatomical study of the frontotemporal-zygomatic arch approach to the superior petroclival region.

The aim of this study was to explore the microsurgical anatomy of the superior petroclival region, and thus provide an anatomical basis for operative approaches. The frontotemporal-orbitozygomatic approach was performed on 20 sides of 10 adult cadaver heads. In comparison to the range of the exposure with the removal of the anterior clinoid process, posterior clinoid process and part of the tip of the petrous bone, we measured the neurovascular course and their relation to the superior petroclival region. We found that the trochlear nerve goes through the edge of the tentorial marginal branch, taking 5.42 mm (4.26-6.96) away from the ophthalmic nerve. Exposing the arteria basilaris, above the middle piece the length of exposure is 15.52 mm (14.22-16.70), resulting in the posterior cerebral artery and the front part of the midbrain being completely exposed. There is little exposure on the front part of the pons and midbrain with a length of 5.6 mm (4.38-6.82). Removing the partial petrosal bones, the inferior segment of the basal artery is exposed, while 4 other nerves cab also be observed: Cranial, abducens, facial and vestibulocochlear. The frontotemporal-zygomatic arch approach can clearly expose the superior petroclival region. Obtaining more information on the relationship between the location of these structures, is therefore helpful in improving the safety and success of surgery in this region.