An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum.

BACKGROUND: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. METHODS: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male ß-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone ß-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes. CONCLUSIONS: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.

Schistosome Infection Impacts Hematopoiesis.

Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. In this article, we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm that causes schistosomiasis. We analyzed the frequency or number of hematopoietic cell types in the bone marrow, spleen, liver, thymus, and blood and observed multiple hematopoietic changes caused by infection. Schistosome infection impaired bone marrow HSC function after serial transplantation. Functional HSCs were present in the infected liver. Infection blocked bone marrow erythropoiesis and augmented spleen erythropoiesis, observations consistent with the anemia and splenomegaly prevalent in schistosomiasis patients. This work defines the hematopoietic response to schistosomiasis, a debilitating disease afflicting more than 200 million people, and identifies impairments in HSC function and erythropoiesis.

CT-based deep learning model: a novel approach to the preoperative staging in patients with peritoneal metastasis.

Peritoneal metastasis (PM) is a frequent manifestation of advanced abdominal malignancies. Accurately assessing the extent of PM before surgery is essential for patients to receive optimal treatment. Therefore, we propose to construct a deep learning (DL) model based on enhanced computed tomography (CT) images to stage PM preoperatively in patients. All 168 patients with PM underwent contrast-enhanced abdominal CT before either open surgery or laparoscopic exploration, and peritoneal cancer index (PCI) was used to evaluate patients during the surgical procedure. DL features were extracted from portal venous-phase abdominal CT scans and subjected to feature selection using the Spearman correlation coefficient and LASSO. The performance of models for preoperative staging was assessed in the validation cohort and compared against models based on clinical and radiomics (Rad) signature. The DenseNet121-SVM model demonstrated strong patient discrimination in both the training and validation cohorts, achieving AUC was 0.996 in training and 0.951 validation cohort, which were both higher than those of the Clinic model and Rad model. Decision curve analysis (DCA) showed that patients could potentially benefit more from treatment using the DL-SVM model, and calibration curves demonstrated good agreement with actual outcomes. The DL model based on portal venous-phase abdominal CT accurately predicts the extent of PM in patients before surgery, which can help maximize the benefits of treatment and optimize the patient's treatment plan.

Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2.

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases and is considered as the most common type of cancer. DLX4 was originally identified as a ß-globin gene suppressor in red blood cells, which plays critical roles in several types of cancers. However, the role and related mechanism of DLX4 in NSCLC are still unclear. The study aimed to uncover the expression of DLX4 in human NSCLC cells and tissues, reveal its possible role in NSCLC, and investigate the underlying mechanisms. Immunoblot and TCGA database were used to detect the expression of DLX4 in human NSCLC cells and tissues. CCK-8, colony formation, and FCM assays were conducted to detect the effects of DLX4 on the viability and cell cycle of NCI-H2170 and A549 cells. Immunoblot assays were further performed to investigate the possible mechanism underlying DLX4 affecting the growth of NSCLC. We revealed that knockdown of DLX4 inhibited NSCLC cell proliferation. We further revealed that DLX4 knockdown induced the NSCLC cell cycle arrest. Our results further showed that downregulation of DLX4 suppressed YB-1 expression, which further suppressed CKS2 expression, thereby suppressing tumor growth of NSCLC. In conclusion, DLX4 has the potential to serve as a promising drug for NSCLC treatment.

Identification of a novel RSRC1-ALK (R6: A20) fusion using next-generation sequencing technique.

Non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) fusion showed promising responses to ALK tyrosine kinase inhibitors (TKIs). In this study, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next generation sequencing (NGS) and Sanger sequencing were performed to identify the presence of ALK fusion, to investigate whether the patient may benefit from TKI therapy. Postoperative pathological analysis indicated invasive adenocarcinoma with mainly mucinous type and partial micropapillary type in left lower lung. Minimally invasive adenocarcinoma was seen in left upper lung, with mainly acinar type. NGS detected a novel RSRC1-ALK (R6: A20) fusion in left lower lobe sample, which was presented as the fusion of exon 6 of RSRC1 and exon 20 of ALK gene. Sanger sequencing validated the fusion. Break rearrangement signal of ALK gene was detected in 80% of tumor cells. Immunohistochemistry showed ALK positive expression in lung. For the treatment, the patient received ensartinib hydrochloride with a dose of 225 mg per day. He was in a state of progression-free survival for at least 24 months in follow-up with no complications. NGS can be used for exploring treatment options for NSCLC patients with ALK fusion.

Testicular Fibrous Pseudotumor: A Benign Disease That Can Be Treated With Testis-Sparing Surgery: A Case Report and Literature Review.

Testicular fibrous pseudotumor is a rare benign disease that is often misdiagnosed as testicular malignancy before surgery. We present a case of a 38-year-old male who had painless palpable masses in the left scrotum. Testicular tumor marker levels were within normal limits, and ultrasound revealed paratesticular masses. Intraoperative rapid diagnosis indicated a fibrous pseudotumor without malignancy. We successfully removed all the masses, along with the testis and a portion of the spermatic cord sheath, avoiding unnecessary orchiectomy.

The role of three-dimensional model in preoperative communication before partial nephrectomy and postoperative management.

Objective: To investigate the role of the three-dimensional (3D) image reconstruction technique in preoperative communication before partial nephrectomy (PN) and postoperative follow-up. Methods: A retrospective study was performed with 158 renal cancer patients treated with PN at our center from May 1, 2017 to April 30, 2019. 81 patients (group A) had preoperative communication using the 3D reconstruction technique, while 77 patients (group B) did not. The surgeon explained the anatomical structure, tumor characteristics, and surgical approach in detail to the two groups of patients. Each patient completed a questionnaire. The loss to follow-up rate over a 3-year period was counted for both groups, and non-cancer-related serious complications such as renal failure and cardio-cerebrovascular disease were observed. This research did not include patients who returned for follow-up care owing to associated complications such as postoperative chronic kidney disease. Comparisons between two groups were performed using the Mann-Whitney U test and chi-square test. Results: All patients showed no statistically significant differences in basic clinical parameters, such as age, gender, body mass index, tumor size, and R.E.N.A.L. score (P â€‹> â€‹0.05). In group A, patients were significantly more likely to experience understanding of renal anatomy (P â€‹= â€‹0.001), characteristics of renal cell carcinoma (P â€‹= â€‹0.003), surgical approach (P â€‹= â€‹0.007), and relief of preoperative anxiety (P â€‹= â€‹0.013). The follow-up adherence at 3 years postoperatively in group A and group B was 21 cases and 10 cases, respectively (P â€‹= â€‹0.041). In addition, glomerular filtration rate < 60 â€‹mL/min/1.73 â€‹m2 or serum creatinine > 186 â€‹µmol/L at 3 years after surgery occurred in 5 patients in group A and 13 in group B (P â€‹= â€‹0.034), and a systolic blood pressure rise greater than 20 â€‹mmHg occurred in 9 patients in group A and 18 in group B (P â€‹= â€‹0.041). Conclusions: The use of 3D reconstruction techniques for preoperative communication can successfully improve patients' perception and comprehension of kidney tumors and PN, as well as help to prevent serious postoperative non-cancer-related complications.

Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer.

Lung cancer is rare in young people, but the incidence and mortality are on the rise. We retrospectively analyzed the data of young patients aged ≤45 years diagnosed as lung cancer in our hospital from 2014 to 2021. The purpose was to explore the clinicopathological characteristics of young patients, and the risk factors affecting overall survival (OS) time. The results showed that the young patients were mainly female, had no smoking history, asymptomatic at initial diagnosis, with a high proportion of adenocarcinoma and stage I-II. We divided all patients into two groups according to age and found that the proportion of stage I-II in 18-35 years group was significantly higher than that in 36-45 years group (P = 0.021). The main manifestation of tumor was ground glass opacity (GGO) in 18-35 years group, while most showed non-GGO in 36-45 years group (P = 0.003). The proportion of minimally invasive adenocarcinoma was higher in 18-35 years group, while the invasive adenocarcinoma was higher in 36-45 years group (P = 0.004). Univariate analysis showed that asymptomatic, stage I-II, surgery, women, with few or no metastatic organs had longer OS. Multivariate analysis showed that the independent factors affecting the OS of young patients were tumor stage and more metastatic organs.

Helminth infection impacts hematopoiesis.

Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. Here we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm which causes schistosomiasis. We analyzed the frequency or number of hematopoietic cell types in the bone marrow, spleen, liver, thymus, and blood, and observed multiple hematopoietic changes caused by infection. Schistosome infection impaired bone marrow HSC function after serial transplantation. Functional HSCs were present in the infected liver. Infection blocked bone marrow erythropoiesis and augmented spleen erythropoiesis, observations consistent with the anemia and splenomegaly prevalent in schistosomiasis patients. This work defines the hematopoietic response to schistosomiasis, a debilitating disease afflicting more than 200 million people, and identifies impairments in HSC function and erythropoiesis.

A metabotropic glutamate receptor affects the growth and development of Schistosoma japonicum.

Schistosomiasis is a zoonotic parasitic disease caused by schistosome infection that severely threatens human health. Therapy relies mainly on single drug treatment with praziquantel. Therefore, there is an urgent need to develop alternative medicines. The glutamate neurotransmitter in helminths is involved in many physiological functions by interacting with various cell-surface receptors. However, the roles and detailed regulatory mechanisms of the metabotropic glutamate receptor (mGluR) in the growth and development of Schistosoma japonicum remain poorly understood. In this study, we identified two putative mGluRs in S. japonicum and named them SjGRM7 (Sjc_001309, similar to GRM7) and SjGRM (Sjc_001163, similar to mGluR). Further validation using a calcium mobilization assay showed that SjGRM7 and SjGRM are glutamate-specific. The results of in situ hybridization showed that SjGRM is mainly located in the nerves of both males and gonads of females, and SjGRM7 is principally found in the nerves and gonads of males and females. In a RNA interference experiment, the results showed that SjGRM7 knockdown by double-stranded RNA (dsRNA) in S. japonicum caused edema, chassis detachment, and separation of paired worms in vitro. Furthermore, dsRNA interference of SjGRM7 could significantly affect the development and egg production of male and female worms in vivo and alleviate the host liver granulomas and fibrosis. Finally, we examined the molecular mechanisms underlying the regulatory function of mGluR using RNA sequencing. The data suggest that SjGRM7 propagates its signals through the G protein-coupled receptor signaling pathway to promote nervous system development in S. japonicum. In conclusion, SjGRM7 is a potential target for anti-schistosomiasis. This study enables future research on the mechanisms of action of Schistosomiasis japonica drugs.

Robot-assisted versus conventional laparoscopic partial nephrectomy for renal hilar tumors: Parenchymal preservation and functional recovery.

OBJECTIVE: To determine whether robot-assisted laparoscopic partial nephrectomy (RALPN) can benefit patients in terms of functional recovery in the treatment of renal hilar tumors compared to conventional laparoscopic partial nephrectomy (CLPN). METHODS: Between January 2019 and July 2021, patients with hilar tumors who underwent partial nephrectomy (PN) were acquired at our center and were classified into RALPN and CLPN groups. Ipsilateral parenchymal volume (IPV) and glomerular filtration rate (GFR) were determined independently 3-5 days before and 3 months after PN using contrast-enhanced computed tomography and nuclear renal scans. Pearson correlation was used to determine the link between ipsilateral GFR preservation and IPV preserved. Concurrently, multivariable analysis was employed to determine characteristics associated with functional recovery. RESULTS: A total of 96 patients with hilar tumors were studied, of which 41 received RALPN and 55 received CLPN. Excisional parenchymal volume was 27 and 37 cm3 (p = 0.005) in RALPN and CLPN groups, respectively, and IPV preserved was 77% and 68% (p < 0.001). Furthermore, the ipsilateral GFR preserved was 77.7% and 75.3%, respectively (p = 0.003). On Pearson correlation, ipsilateral GFR preservation was linked with IPV preserved (r = 0.36, p < 0.001). According to a multivariate study, baseline GFR, IPV preserved, and surgical procedures (RALPN vs. CLPN) were significant factors influencing functional recovery. CONCLUSION: Our study suggests that RALPN, rather than CLPN, can achieve better functional recovery in the treatment of hilar tumors due to its ability to win more IPV preserved. RALPN should be recommended as the first-line treatment for hilar tumors, but randomized controlled trials are required to validate our findings.

A male-derived nonribosomal peptide pheromone controls female schistosome development.

Schistosomes cause morbidity and death throughout the developing world due to the massive numbers of eggs female worms deposit into the blood of their host. Studies dating back to the 1920s show that female schistosomes rely on constant physical contact with a male worm both to become and remain sexually mature; however, the molecular details governing this process remain elusive. Here, we uncover a nonribosomal peptide synthetase that is induced in male worms upon pairing with a female and find that it is essential for the ability of male worms to stimulate female development. We demonstrate that this enzyme generates ß-alanyl-tryptamine that is released by paired male worms. Furthermore, synthetic ß-alanyl-tryptamine can replace male worms to stimulate female sexual development and egg laying. These data reveal that peptide-based pheromone signaling controls female schistosome sexual maturation, suggesting avenues for therapeutic intervention and uncovering a role for nonribosomal peptides as metazoan signaling molecules.

Prognostic Significance of Membranous Carbonic Anhydrase IX Expression in Patients with Nonmetastatic Clear Cell Renal Cell Carcinoma of Different Tumor Stages.

Background: There are paradoxical results regarding whether carbonic anhydrase IX (CAIX) is a prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). The objective of this study was to evaluate prognostic significance of CAIX in nonmetastatic ccRCC patients of different stages. Materials and Methods: This is a retrospective study on 1263 patients with nonmetastatic ccRCC from January 2005 to June 2018. Patients were stratified into eight subgroups (pT1a, pT1b, pT2a, pT2b, pT3a, pT3b, pT3c, and pT4) according to the 2016 TNM classification system. Immunohistochemical staining of membranous CAIX was quantified. Cancer-specific survival (CSS) rates in patients with high (>85%) and low (<85%) CAIX expressions were compared by Kaplan-Meier curves with log-rank test. Results: There were 220 tumors (17.42%) with low CAIX expression and 1043 tumors (82.58%) with high CAIX expression. The cumulative CSS rates were statistically significant between all patients with low and high CAIX expression (p-value <0.001). In pT2a, pT2b, and pT3a subgroups, the patients with low CAIX expression exhibited markedly decreased cumulative CSS rates compared to patients with high CAIX expression (p-value <0.05). Univariable and multivariable Cox regression analysis showed that CAIX expression was an independent predictor of prognosis in patients with pT2a, pT2b, and pT3a ccRCC (p-value <0.05), rather than in all nonmetastatic patients. Conclusion: CAIX expression is of independent prognostic value for ccRCC patients in pT2a, pT2b, and pT3a stages. CAIX expression combined with tumor stage would further improve risk stratification of nonmetastatic ccRCC patients and provide directions for therapies.

Mirabegron improves the irritative symptoms caused by BCG immunotherapy after transurethral resection of bladder tumors.

BACKGROUND: This study aims to explore the efficacy and safety of mirabegron in treating irritative symptoms induced by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumors (TURBT). METHODS: A total of 160 patients subjected to TURBT was randomly divided into the mirabegron group and placebo group with 80 patients in each group. Then, the patients were administered 25 mg mirabegron or placebo daily, starting the first day after BCG infusion. The first BCG perfusion was conducted at least 2 weeks after TURBT. The 3-day bladder diaries were completed in all patients, 1 day before BCG perfusion, and on the 1st, 6th, and 13th days after the first BCG perfusion. Overactive bladder symptom scores were completed 1 day before BCG perfusion, and on the 6th and 13th days after the first BCG perfusion. RESULTS: Symptom scores of bladder hyperactivity were significantly different between the two groups (p < 0.001). Also, the frequency of nocturia, pollakiuria, micturition urgency, urinary incontinence and was significantly lower in group 1 than that in group two (p < 0.05). CONCLUSION: Our findings demonstrate that mirabegron is a valuable clinical drug for the management of irritative symptoms after TURBT with subsequent intravesical BCG perfusion.

The second to fourth digit ratio (2D:4D): A risk factor of bladder cancer in men.

BACKGROUND: Exposure to prenatal sex steroids as indicated by the ratio of the second to fourth digit length (2D:4D) has been linked to the risk of onset of cancer, while sex steroids may expand the gender disparity in bladder cancer (BC) morbidity. AIM: To explore the association between 2D:4D ratio and BC risk. SUBJECTS: 307 bladder cancer patients and 321 cancer-free individuals. OUTCOME MEASURES: Relationships between 2D:4D and incidence of bladder cancer. RESULTS: For males, a lower 2D:4D ratio of both hands was obtained in the BC group, relative to the control group (left hand: 0.940 ± 0.031 vs. 0.954 ± 0.024, t = -4.72, p < 0.001, Cohen's d = 0.491 and right hand: 0.939 ± 0.031 vs. 0.952 ± 0.022, t = -4.493, p < 0.001, Cohen's d = 0.511). In females, no differences in the 2D:4D ratio were observed between the BC and control groups (p > 0.05). Correlation analysis between 2D:4D ratio and pathological index found no correlation among the BC grade or stage (p > 0.05). CONCLUSION: Men with BC have a lower 2D:4D ratio compared with healthy men. Therefore, having a low 2D:4D ratio is a risk factor for BC in men. Prenatal exposure to sex steroids might play a role in the etiology of BC, which could partially explain the gender disparity in the prevalence of BC.

Efficacy and Safety of Combination Comprising Tamsulosin and PDE5-Is, Relative to Monotherapies, in Treating Lower Urinary Tract Symptoms and Erectile Dysfunction Associated With Benign Prostatic Hyperplasia: A Meta-Analysis.

We report safety and efficacy of a combination therapy, comprising tamsulosin and phosphodiesterase type 5 inhibitors (PDE5-Is), relative to monotherapy, to ascertain its potential in treating lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) secondary to benign prostatic hyperplasia (BPH) after 3 months' treatment. We screened MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases, for randomized controlled trials, and obtained eight articles comprising 1144 participants. Results showed that the combination group had superior outcomes with regard to International Prostate Symptom Score (IPSS) and Qmax, compared to the other two groups. The combination group also had superior efficacy with regard to International Index of Erectile Function (IIEF) than the tamsulosin group, but not over the PDE5-Is group. Further, the combination group showed better efficacy in IPSS voiding and quality of life (QoL) compared to the PDE5-Is group. An analysis of safety outcomes revealed extremely high adverse events (AEs) and pain in the combination group. However, therapy discontinuation due to pain and AEs did not increase with increase in AEs. Overall, our findings indicate that a combination of tamsulosin and PDE5-Is is superior to individual tamsulosin and PDE5-Is monotherapy, with regard to improving LUTS and ED secondary to BPH.

Complete retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma without patient repositioning: a single-center experience.

OBJECTIVE: This study was performed to evaluate the outcome of complete retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision (RLNU-BCE), which is performed to treat urothelial carcinomas in the renal pelvis or in the ureter higher than the crossing of the common iliac artery without patient repositioning. METHODS: We retrospectively analyzed the clinical data of 48 patients with upper tract urothelial carcinoma who underwent complete RLNU-BCE in our institution from May 2017 to September 2019. RESULTS: RLNU-BCE was successfully performed in all 48 patients. The median operation time was 110 minutes [interquartile range (IQR), 100-130 minutes], and the median postoperative anesthesia recovery time was 10 minutes (IQR, 7-15 minutes). The median postoperative hospitalization period was 5 days (IQR, 4-6 days). Pathologic examination revealed that the margin of all resected specimens was negative. After a median follow-up of 13 months (IQR, 7-20 months), no local recurrence or distant metastasis was found. No complications occurred during follow-up. CONCLUSION: Based on our experience with this technique, RLNU-BCE deserves application and promotion in clinical practice. Long-term comparative studies are required to confirm its superiority over other techniques.

Systematic Review and Meta-Analysis of the Efficacy and Safety of Enhanced Recovery After Surgery vs. Conventional Recovery After Surgery on Perioperative Outcomes of Radical Cystectomy.

Background and objective: Radical cystectomy has been characterized as the most difficult operation in urology because of the complex surgical procedures and postoperative complications. Enhanced recovery after surgery (ERAS), which reduces the incidence of perioperative complications, has been widely used in clinical surgery. Herein, we performed a meta-analysis to evaluate the efficacy and safety of ERAS vs. conventional recovery after surgery (CRAS) on perioperative outcomes of radical cystectomy. Methods: We performed a systematic search of randomized controlled trials (RCTs) in the following databases: Medline, Embase, and the Cochrane Controlled Trials Register, based on the PICOS strategy. The reference lists of the retrieved studies were further surveyed for relevant publications. Results: Our search yielded seven RCTs containing 813 patients. The ERAS group was found to have better performance in the following parameters: length of hospital stay [mean difference (MD) = -1.12, 95% confidence interval (CI): -1.80 to -0.45, P = 0.001], time to first flatus (MD = -0.70, 95% CI: -0.98 to 0.41, P < 0.00001), and time to regular diet (MD = -0.12, 95% CI: -1.76 to -0.28, P = 0.007). However, there were no significant differences between the two groups in major complications [odds ratio (OR) = 0.91, 95% CI: 0.63 to 1.34, P = 0.64], readmission (OR = 1.15, 95% CI: 0.65 to 2.01, P = 0.63), ileus (OR = 0.75, 95% CI: 0.44 to 1.28, P = 0.29), wound infection (OR = 0.56, 95% CI: 0.31 to 1.01, P = 0.05), mortality (OR = 0.69, 95% CI: 0.24 to 1.99, P = 0.49), or time to first bowel movement (MD = -0.55, 95% CI: -1.62 to 0.53, P = 0.32). Conclusion: ERAS reduced the length of hospital stay, time to first flatus, and time to regular diet after cystectomy. Compared to CRAS protocols, ERAS protocols do not increase the risk of adverse events.

Schistosoma japonicum cathepsin B2 (SjCB2) facilitates parasite invasion through the skin.

Cercariae invasion of the human skin is the first step in schistosome infection. Proteases play key roles in this process. However, little is known about the related hydrolytic enzymes in Schistosoma japonicum. Here, we investigated the biochemical features, tissue distribution and biological roles of a cathepsin B cysteine protease, SjCB2, in the invasion process of S. japonicum cercariae. Enzyme activity analysis revealed that recombinant SjCB2 is a typical cysteine protease with optimum temperature and pH for activity at 37°C and 4.0, respectively, and can be totally inhibited by the cysteine protease inhibitor E-64. Immunoblotting showed that both the zymogen (50 kDa) and mature enzyme (30.5 kDa) forms of SjCB2 are expressed in the cercariae. It was observed that SjCB2 localized predominantly in the acetabular glands and their ducts of cercariae, suggesting that the protease could be released during the invasion process. The protease degraded collagen, elastin, keratin, fibronectin, immunoglobulin (A, G and M) and complement C3, protein components of the dermis and immune system. In addition, proteomic analysis demonstrated that SjCB2 can degrade the human epidermis. Furthermore, it was showed that anti-rSjCB2 IgG significantly reduced (22.94%) the ability of the cercariae to invade the skin. The cysteine protease, SjCB2, located in the acetabular glands and their ducts of S. japonicum cercariae. We propose that SjCB2 facilitates skin invasion by degrading the major proteins of the epidermis and dermis. However, this cysteine protease may play additional roles in host-parasite interaction by degrading immunoglobins and complement protein.

Oxidized Low Density Lipoprotein-Induced Atherogenic Response of Human Umbilical Vascular Endothelial Cells (HUVECs) was Protected by Atorvastatin by Regulating miR-26a-5p/Phosphatase and Tensin Homolog (PTEN).

BACKGROUND Atherosclerosis is a chronic and multifactorial disease, and it is the main reason of coronary heart disease, cerebral infarction, and peripheral vascular disease, which leads to the formation of lesions in arterial blood vessels. Our study aimed to explore the protective effect and its underlying mechanism of atorvastatin (ATV) on oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis. MATERIAL AND METHODS Human umbilical vascular endothelial cells (HUVECs) were cultured and pretreated with ox-LDL to establish an in vitro atherosclerotic cell model. Cell Counting Kit-8 (CCK-8) assay, TUNEL staining, and Transwell assay were used to detect the cell activity, apoptosis, and migration in HUVECs. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to measure the mRNA and protein expressions of adhesion-related genes in HUVECs. RESULTS Pretreated with 100 mg/L ox-LDL resulted in a 57.23% decrease of cell viability and 81.09% increase of apoptotic injury in HUVECs compare to the control. Meanwhile, ox-LDL pretreatment increased the cell migration and the expression of miR-26a-5p in HUVECs. ATV treatment could effectively reverse the cellular damage induced by ox-LDL, decrease the release of adhesion-related molecules, and downregulate the expression of miR-26a-5p by 44.79% in HUVECs. Moreover, phosphatase and tensin homolog (PTEN) was demonstrated to be the target gene of miR-26a-5p. CONCLUSIONS Our results highlight that ATV protects against ox-LDL-induced downregulation of cell viability, upregulation of cell apoptosis, migration, as well as the release of adhesion-related molecules in HUVECs through the miR-26a-5p/PTEN axis. This study provides new insights into the underlying mechanism of ATV therapeutic potential in atherosclerosis, and also provides a new strategy for the treatment of atherosclerosis.