CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition.

EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC) suffering from the EGFR mutation. Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome. In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells. CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib. Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis. To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1. Moreover, FOSL1 transcriptionally regulated CIB2 expression. Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo. Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.

Progression of Uterine Artery Pseudoaneurysm Documented by Ultrasonography: A Case Report.

Introduction: Uterine artery pseudoaneurysm (UAP) is a rare cause of late postpartum hemorrhage. Insufficient understanding of this condition among clinicians may result in delayed diagnosis and treatment, potentially leading to incorrect interventions and poor prognosis, including fatal hemorrhage and even necessitating hysterectomy in severe cases. Case Report: The patient, a 41-year-old woman with a history of three pregnancies and two deliveries, underwent cesarean section and subsequently experienced persistent small amounts of vaginal bleeding for a duration of two months. Transvaginal ultrasonography revealed a hypoechoic mass in the cervix that was initially misdiagnosed as a cervical fibroid. Approximately 12 h prior to admission, she experienced an episode of acute vaginal bleeding of significant intensity. Emergency transvaginal ultrasound demonstrated an intrauterine mass located in the posterior wall of the cervix with swirling blood flow, exhibiting a to-and-fro pattern. The mass was connected to the left uterine artery adjacent to the cervix through a tear measuring approximately 0.5 cm in diameter. Emergency bilateral uterine artery embolization was performed. After a follow-up period of ten months, there was no recurrence of abnormal vaginal bleeding, and subsequent ultrasound examination confirmed the complete resolution of the cervical lesions. Conclusion: The findings of this case suggest that the UAP undergoes a dynamic process. In the early stages, the lesion may manifest as a small hypoechoic or anechoic area within the myometrium. Color Doppler imaging might not reveal blood flow signals within the lesion, potentially leading to misdiagnosis as other common uterine lesions such as fibroids or cysts. However, considering the close association between UAP and the uterine artery, meticulous observation of the relationship between the uterine artery and its branches is crucial for identifying myometrial lesions to facilitate early detection of UAP and minimize misdiagnosis.

Potential planting regions of Pterocarpus santalinus (Fabaceae) under current and future climate in China based on MaxEnt modeling.

This study modeled the habitat distribution of Pterocarpus santalinus, a valuable rosewood species, across China under current and future climate scenarios (SSPs126, SSPs245, and SSPs585) using MaxEnt. Our findings reveal that the current suitable habitat, spanning approximately 409,600 km2, is primarily located in the central and southern parts of Guangdong, Guangxi, Fujian, and Yunnan, as well as in the Hainan provinces, along with the coastal regions of Taiwan, and the Sichuan-Chongqing border. The habitat's distribution is significantly influenced by climatic factors such as temperature seasonality (bio4), mean temperature of the wettest quarter (bio8), annual mean temperature (bio1), and annual precipitation (bio12), while terrain and soil factors play a lesser role. Under future climate scenarios, the suitable habitat for P. santalinus is projected to expand, with a northeastward shift in its distribution center. This research not only sheds light on the geoecological characteristics and geographical distribution of P. santalinus in China but also offers a scientific basis for planning its cultivation areas and enhancing cultivation efficiency under changing climate conditions.

HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

Right gastroepiploic artery length determined anastomotic leakage after minimally invasive esophagectomy for esophageal cancer: a prospective cohort study.

BACKGROUND: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined. MATERIALS AND METHODS: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms. RESULTS: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88 vs. 8.84%, P =0.01). Multivariable binary logistic regression identified Group SR and LR (odds ratio: 2.651, 95% CI: 1.124-6.250, P =0.03) and Neoadjuvant therapy (odds ratio: 2.479, 95% CI: 1.374-4.473, P =0.00) as independent predictors of AL. CONCLUSIONS: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk.

Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort.

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.

Comparison of two different methods for lymphadenectomy along the left recurrent laryngeal nerve by minimally invasive esophagectomy in patients with esophageal squamous cell carcinoma: a prospective randomized trial.

BACKGROUND: Lymph nodes along the left recurrent laryngeal nerve (LRLN) is thought to be highly involved in esophageal cancer. Given the unique anatomical positioning of the nerve, performing lymphadenectomy in this region requires advanced techniques within limited working space. Meanwhile, high incidence of morbidity and mortality is associated with lymphadenectomy. Although several methods have been applied to reduce the technical requirement and the incidence of postoperative complication, the optimal method remains controversial. METHODS: This study was a single-center, prospective, randomized trial to investigate the utility of lymphadenectomy along the LRLN during the minimally invasive esophagectomy in esophageal squamous cell carcinoma patients by comparing the surgical outcome, postoperative complication, survival rate, and quality of life (QoL) between the retraction method (RM) and the suspension method (SM) in patients with esophageal cancer from June 2018 to November 2020. QoL was assessed according to questionnaire: EQ-5D-5L. RESULTS: Of 94 patients were enrolled and randomized allocated to RM and SM group equally. Characteristics did not differ between groups. The duration of lymph node dissection along LRLN was significant longer in SM group ( P <0.001). No difference was observed about postoperative complications. One of in-hospital death was occurred in each group ( P >0.999). Patients in neither of groups exhibiting difference about 3-year disease-free survival rate ( P =0.180) and overall survival rate ( P =0.430). No difference was observed in postoperative QoL between groups at different time points (all, P >0.05). CONCLUSION: Both methods of lymph node dissection along the LRLN during minimally invasive esophagectomy in esophageal squamous cell carcinoma patients are technically feasible and safe. The RM appears more favorable in terms of reducing surgical duration compared to the SM.

Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

Impact of perioperative decreased serum albumin level on anastomotic leakage in esophageal squamous cell carcinoma patients treated with neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined. METHODS: The data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups. RESULTS: After exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277). CONCLUSIONS: Severely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4 .

A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.

Objective: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA. Materials and methods: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed. Result: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets. Conclusion: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.

[Hyperspectral imaging technology distinguishes between Puerariae Lobatae Radix and Puerariae Lobatae Caulis].

Puerariae Lobatae Radix, the dried root of Pueraria lobata, is a traditional Chinese medicine with a long history. Puerariae Lobatae Caulis as an adulterant is always mixed into Puerariae Lobatae Radix for sales in the market. This study employed hyperspectral imaging(HSI) to distinguish between the two products. VNIR lens(spectral scope of 410-990 nm) and SWIR lens(spectral scope of 950-2 500 nm) were used for image acquiring. Multi-layer perceptron(MLP), partial least squares discriminant analysis(PLS-DA), and support vector machine(SVM) were employed to establish the full-waveband models and select the effective wavelengths for the distinguishing between Puerariae Lobatae Caulis and Puerariae Lobatae Radix, which provided technical and data support for the development of quick inspection equipment based on HSI. The results showed that MLP model outperformed PLS-DA and SVM models in the accuracy of discrimination with full wavebands in VNIR, SWIR, and VNIR+SWIR lens, which were 95.26%, 99.11%, and 99.05%, respectively. The discriminative band selection(DBS) algorithm was employed to select the effective wavelengths, and the discrimination accuracy was 93.05%, 98.05%, and 98.74% in the three different spectral scopes, respectively. On this basis, the MLP model combined with the effective wavelengths within the range of 2 100-2 400 nm can achieve the accuracy of 97.74%, which was close to that obtained with the full waveband. This waveband can be used to develop quick inspection devices based on HSI for the rapid and non-destructive distinguishing between Puerariae Lobatae Radix and Puerariae Lobatae Caulis.

PxRdl2 dsRNA increased the insecticidal activities of GABAR-targeting compounds against Plutella xylostella.

The utilization of RNA interference (RNAi) for pest management has garnered global interest. The bioassay results suggested the knockout of the PxRdl2 gene significantly increased the insecticidal activities of the γ-aminobutyric acid receptor (GABAR)-targeting compounds (fipronil, two pyrazoloquinazolines, and two isoxazolines), thereby presenting a viable target gene for RNAi-mediated pest control. Consequently, we suggest enhancing the insecticidal activities of GABAR-targeting compounds by knockdown the transcript level of PxRdl2. Furthermore, PxRdl2 dsRNA was expressed in HT115 Escherichia coli to reduce costs and protect dsRNA against degradation. In comparison to in vitro synthesized dsRNA, the recombinant bacteria (ds-B) exhibited superior interference efficiency and greater stability when exposed to UV irradiation. Collectively, our results provide a strategy for insecticide spray that combines synergistically with insecticidal activities by suppressing PxRdl2 using ds-B and may be beneficial for reducing the usage of insecticide and slowing pest resistance.

Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.

Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway.

Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.

Safety and feasibility of three-dimensional McKeown minimally invasive esophagectomy.

BACKGROUND: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE. METHODS: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors. RESULTS: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively. CONCLUSION: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases.

Thermal conductivity and mechanical properties of graphite/Mg composite with a super-nano CaCO3 interfacial layer.

Incorporating graphite/graphene into a Mg alloy matrix is a promising approach for developing lightweight heat dissipation materials. However, carbon material is inherently incompatible with Mg because of their distinctly different surface characteristics, resulting in the challenge of composite fabricating and interface controlling. Herein, a new strategy of in situ interfacial modification was proposed to achieve excellent thermal conductivity and mechanical properties in graphite/Mg composites. A super-nano CaCO3 interfacial layer was reported in this paper. The detailed interfacial structure, reaction thermodynamics and kinetics, and interface strengthening mechanisms were analyzed and discussed. Several preferential epitaxial relationships of the Mg/CaCO3 interface were revealed, which are conducive to minimize the interfacial energy, stabilize and strengthen the interface. Moreover, strong ionic bond of graphite/CaCO3 interface was demonstrated. The strong chemical interface bonding of graphite-Mg via in situ interface modification facilitates both the interfacial cohesion and interfacial thermal conduction, which endows the graphite/Mg composites with superior strength-thermal conductivity synergy.

Improving bowel preparation for colonoscopy with a smartphone application driven by artificial intelligence.

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.

MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression.

Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. Although recent studies have shed insights on the potential causes of male infertility, its underlining mechanisms still remain to be elucidated. We developed a Mrkn2 knockout mice model to study this gene and found that deletion of Mkrn2 in mice led to male infertility. Interestingly, the expression level of signal transducer and activator of the transcription (STAT)1 was significantly decreased in MKRN2 knockout testis and MEF cells. Co-IP assay showed an interaction between MKRN2 and STAT1. Moreover, our results further indicated that MKRN2 regulated the expression level of SIX4 and tenascin C (TNC) via the EBF transcription factor 2 (EBF2) in mice. The results of our study will provide insights into a new mechanism of male infertility.

Effect of pleural adhesions on short- and long-term outcomes after minimally invasive esophagectomy: a propensity score matching analysis.

BACKGROUND: The extent to which the presence of pleural adhesions affects the surgical and oncological outcomes of patients undergoing McKeown minimally invasive esophagectomy (MIE) for esophageal cancer (EC) has not previously been studied. METHODS: Data of consecutive EC patients undergoing McKeown MIE by a single surgeon in the Department of Thoracic Surgery at Daping Hospital from November 2015 to December 2020 were collected. Patients were grouped according to the presence or absence of pleural adhesions when entering the chest cavity. Propensity score matching (PSM) was used to reduce selection bias from confounding factors. Kaplan-Meier was used to assess the survival differences. RESULTS: A total of 617 consecutive EC patients underwent McKeown MIE were enrolled. There were 116 patients with pleural adhesions (Group A) and 501 patients without pleural adhesions (Group B). Patients in Group A were more likely to be older than those of patients in Group B: (66.26 vs. 63.27, P = 0.001). In addition, Group A had more patients with chronic obstructive pulmonary disease (COPD) (24.1% vs. 16.8%, P = 0.04). After propensity score matching (102 matched patients in Group A and 185 matched patients in Group B), these findings were no longer statistically significant. Postoperative pulmonary infection occurred in 57 patients in Group A and in 15 patients in Group B (53.9% vs. 13.0%, P < 0.001). In addition, the presence of pleural adhesions was significantly associated with the prolonged operation time (232 min vs. 210 min, P < .001), length of stay (12 days vs. 10 days, P = 0.001), and hydrothorax requiring drainage (12.7% vs. 5.4%, P = 0.04). However, the disease-specific survival and disease-free survival rates were comparable between the two groups (P = 0.40 and 0.13, respectively). CONCLUSIONS: The presence of pleural adhesions predicted an increased operation time, length of stay, postoperative pneumonia, and hydrothorax requiring drainage of EC patients undergoing McKeown MIE, but did not exert unfavourable effect on long-term survival.

Cloning, Prokaryotic Expression and Functional Characterization of NifH Gene from the Associative Nitrogen-Fixing Bacteria Klebsiella Variicola DX120E.

Background: Biological nitrogen fixation (BNF) is a unique mechanism in which microorganisms utilize the nitrogenase enzyme to catalyze the conversion of atmospheric nitrogen (N2) to ammonia (NH3). Fe protein, encoded by the nifH gene, is an essential component of the nitrogenase in Klebsiella variicola DX120E. However, the function of this gene in regulating nitrogen fixing activity is still unclear. Objectives: The objective of this study was to reveal the function of nifH gene in associative nitrogen-fixing bacteria Klebsiella variicola DX120E and micro-sugarcane system by immunoassay and gene editing. Materials and Methods: In the current investigation, the nifH gene was cloned in a pET-30a (+) vector and expressed in Escherichia coli. The NifH protein was purified and used to immunize rabbit, and then the serum was collected and purified to obtain rabbit anti-NifH polyclonal antibodies. The CRISPR-Cas9 system was applied to produce nifH mutant strains, and the nitrogen-fixing enzyme activity, gene, and protein expression were analyzed. Results: Both in vitro and in vivo NifH proteins were detected by Western blotting, which were 43 and 32 kDa respectively. The expression of nifD and nifK genes was decreased, and nitrogenase activity was reduced in the nifH mutant strain. Conclusion: The nifH gene mutant weakened the nitrogenase activity by regulating the expression of Fe protein, which suggests a potential strategy to study the nitrogen fixation-related genes and the interactions between endophytic nitrogen-fixing bacteria and sugarcane.