The carrier function and inhibition effect on benign prostatic hyperplasia of a glucan from Epimedium brevicornu Maxim.

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.

Establishing an animal model for peritoneal catheter malfunction caused by omental wrapping using negative pressure suction: in vitro and in vivo exploration.

BACKGROUND: This study aims to establish a simplified and effective animal model of catheter malfunction caused by omental wrapped using negative pressure suction. METHOD: The peritoneal dialysis catheter outlet was linked to a negative-pressure (0-75mmHg) suction pump to intensify the negative pressure. Different negative pressures were tested for model construction in vitro. In vivo, a model of peritoneal catheter malfunction caused by omental wrapped was constructed in five beagles after catheter placement. Catheter drainage conditions and related complications were monitored before and after the model establishment. RESULTS: In the vitro experiment, the overall success rate of constructed models was 90% (36/40). The total malfunction rate was higher in 62.5 mmHg (10/10) and 75 mmHg (10/10) than in 12.5 mmHg (8/10) and 37.5 mmHg (8/10). The outflow velocity of dialysate at 62.5 mmHg was significantly lower than that at 12.5 mmHg and 37.5 mmHg, without a statistically significant difference compared to 75 mmHg. In the in vivo experiment, catheter outflow velocity increased, and residual fluid volume decreased after omental wrapped (99.6 ± 6.7 ml/min vs. 32.6 ± 4.6 ml/min at initial five minutes, p < 0.0001; 69.2 ± 16.3 ml vs. 581.0 ± 109.4 ml, p < 0.001). And the outflow velocity was finally below 2 ml/min. No severe related complications (such as infection, organ damage, or bleeding) were observed through laparoscopic examination and dialysate tests seven days post-operation. CONCLUSION: Utilizing negative pressure suction to increase negative pressure around catheter tip is a simple, safe, and effective method for establishing an animal model of omental wrapped leading to catheter malfunction.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

High performance and recyclable Ag/ZnO/PM substrate for the detection of organic pollutants.

A sensitive and recyclable substrate was fabricated through in situ reduction of silver nanoparticles (NPs) on zinc oxide nanorods (NRs). The prepared silver nanoparticles/zinc oxide nanorods/polyamide mesh (Ag/ZnO/PM) substrate exhibited not only excellent surface-enhanced Raman scattering (SERS) performance to R6G with a limit of detection (LOD) of 10-12 M, mainly attributed to the synergistic effect of the suitable size and the nanoscale gaps of the Ag NPs to produce local surface plasmon resonance (LSPR), but also outstanding self-cleaning property via UV irradiation due to its significant photocatalytic property based on the non-equilibrium carriers generated by ZnO and the presence of Schottky junctions between Ag and ZnO. The substrate showed good recycling stability even after five cycles. Furthermore, the successful recyclable application of Ag/ZnO/PM for tetracycline hydrochloride (TC) detection with high sensitivity further suggested that it is a promising candidate for constructing a portable SERS platform to detect organic pollutants.

A Good Prognosis of Patients with Acute Pancreatitis Combined with Pulmonary Embolism: Early Identification and Intervention.

BACKGROUND: Pulmonary embolism (PE) is a relatively rare vascular complication of acute pancreatitis (AP), and its mortality rate is high. To our knowledge, relevant literature reports still need to be summarized. In this study, we analyzed the clinical characteristics, treatment, and prognosis of five patients with AP complicated by PE and summarized and reviewed the relevant literature. METHODS: Clinical data of patients with AP complicated by PE treated in Taizhou Hospital of Zhejiang Province between January 2017 and September 2022 were retrospectively collected. Combined with the relevant literature, the clinical characteristics, treatment, and prognoses of patients with AP combined with PE were analyzed and summarized. RESULTS: Five patients were eventually enrolled in this study. Among the five patients with AP complicated by PE, all (100%) had symptoms of malaise, primarily chest tightness, shortness of breath, and dyspnea. All patients (100%) had varied degrees of elevated D-dimer levels and a significant decrease in the pressure of partial oxygen (PO2) and pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2/FiO2). Computed tomographic angiography (CTA) or pulmonary ventilation/perfusion imaging revealed a pulmonary artery filling defect in these patients. One patient (20%) had left calf muscular venous thrombosis before the occurrence of PE. Four patients (80%) were treated with lowmolecular- weight heparin (LMWH), and one patient (20%) was treated with rivaroxaban during hospitalization; all continued oral anticoagulant therapy after discharge. All patients (100%) were cured and discharged. No patients showed recurrence of AP or PE. CONCLUSION: PE is a rare but life-threatening complication of AP. However, once diagnosed, early treatment with anticoagulation or radiological interventional procedures is effective, and the prognosis is good. Core Tips: Pulmonary embolism (PE) is a rare but life-threatening complication of acute pancreatitis (AP). Its early diagnosis and timely anticoagulation or radiological intervention can reduce mortality. However, only nine cases have been reported in the English literature thus far, and they are all case reports. Our study is the first systematic analysis of patients with AP combined with PE with a review of the relevant literature. Our patients and those reported in the literature were discharged with good prognoses under treatment such as anticoagulation and vascular intervention. These cases remind clinicians that, in patients with AP, especially those with risk factors for venous thrombosis, it is necessary to monitor the D-dimer level dynamically. Clinicians should pay attention to AP patients' symptoms and related examinations to reduce the chance of a missed diagnosis or misdiagnosis of PE.

Maternal and neonatal outcomes for kidney transplant recipients.

OBJECTIVE: To report pregnancy outcomes for women with kidney transplantation and investigate whether different intervals after transplantation have different effects on pregnancy outcomes. METHODS: A single-center retrospective study was performed. Based on intervals after transplantation, pregnant women with kidney transplantation are divided into two groups: intervals <5 years and ≧5 years. The maternal and neonatal outcomes were compared between the two groups. RESULTS: No maternal and neonatal deaths occurred. The average age of mothers during pregnancy was 32.3 ± 4.1 years and they had a functioning transplant for 4 (interquartile ranges, 3, 6) years. Preeclampsia occurs in sixteen (16.5 %) pregnancies and gestational diabetes (GDM) occurs in twenty (20.6 %). Eighty-eight newborns (90.7 %) had a gestational age of <37 weeks. The average gestational age for live births was 33.8 ± 2.2 weeks and the average birth weight was 2285.6 ± 581.8 g. Neonatal respiratory distress syndrome (NRDS) occurs in fifty-one babies (52.6 %), intraventricular hemorrhage (ICH) occurs in twenty-nine (29.8 %), atrial septal defects (ASD) occurs in thirty-two (32.9 %) and bronchopulmonary dysplasia (BPD) occurs in seven (7.2 %). Further analysis, pregnancy results, including pre-eclampsia, hypertension or GDM, did not differentiate between the two groups (intervals <5 years vs. ≧5 years). Neonatal outcomes, including premature delivery, low birth weight, mode of birth, small for gestational age (SGA), RDS, ICH, ASD, BPD were not distinguishable between the two groups (intervals <5 years vs. ≧5 years). The level of neonatal blood creatinine after birth was linearly related to high maternal creatinine, and can drop to normal levels within a week. CONCLUSIONS: The incidence of maternal and neonatal complications in pregnancies following kidney transplantation is still high, despite the success of most pregnancies. Various posttransplant intervals had no significant impact on pregnancy outcomes.

Ddx5 Targeted Epigenetic Modification of Pericytes in Pulmonary Hypertension After Intrauterine Growth Restriction.

Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. Although there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related pulmonary hypertension and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted using a Sprague-Dawley rat model of IUGR-related pulmonary hypertension. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related pulmonary hypertension, accompanied by weakened endothelial-pericyte interactions. Through whole-transcriptome sequencing, Ddx5 (DEAD-box protein 5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205 (miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of ß-catenin by inhibiting the phosphorylation of Gsk3ß at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate pulmonary hypertension. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205/Ddx5/p-Gsk3ß/ß-catenin axis could be a promising therapeutic approach for IUGR-related pulmonary hypertension.

A generalized fit index for evaluating treatment plans of multiple target volumes with different prescribed dose: Generalized dose distribution fit index.

BACKGROUND AND PURPOSE: The differential fit index (dFI) and cumulative fit index (cFI) were defined in our previous study to evaluate the fit of isodose surfaces to the target volume. They were only applicable to plans for a single target volume. Therefore, this study aimed to generalize these indices for evaluating plans for multiple target volumes and different prescribed doses. MATERIALS AND METHODS: dFI was redefined as the ratio of the integral dose of the volume occupied by an isodose surface to that of the union of all target volumes. cFI was defined as the integral of dFI from a certain dose level of interest to the prescribed dose to be evaluated. To evaluate the performance of the generalized fit index, brain metastasis, head and neck, lung cancer, liver cancer, and cervical cancer cases were selected. For each case, a pair of plans was designed, with one plan having a better fitting dose distribution. The dose fit of these plans was investigated using cFI, the dose gradient index (GI), and the conformity index (CI). RESULTS: In total, 26 pairs of evaluations were performed. The correct evaluation rates for cFI, GI, and CI were 96%, 26.92%, and 92.31%, respectively, illustrating that GI was not valid for evaluating complex plans. CONCLUSIONS: The generalized fit index proved effective for evaluating the dose fit of plans for multiple target volumes with different prescribed doses.

Neonatal outcomes and related risk factors of 30 cases with aplastic anemia in pregnancy: A retrospective study.

OBJECTIVE: To analyze the neonatal outcomes of pregnancies complicated by aplastic anemia (AA) and to investigate the underlying risk factors. METHODS: A single-center retrospective study was performed. Thirty singleton gravidas with AA (AA group) and another thirty singleton gravidas (control group) without immune or blood system disorders who gave birth around the same time were selected. Neonatal outcomes were compared between the two groups. Meanwhile, multivariable analyses were utilized to investigate the association between underlying risk factors and adverse neonatal events. RESULTS: No neonatal deaths occurred. Compared to the control group, the offspring of women with AA had a smaller gestational age (36 ± 1.9 vs. 39.1 ± 0.9 weeks; P < 0.001) and birth weight (2683.7 ± 479.9 vs. 3324.3 ± 394.1 g; P < 0.001). Newborns of women with AA had a higher risk of premature delivery (53.3 % vs. 3.3 %; P < 0.001), low birth weight (23.3 % vs. 0 %; P < 0.001) and NICU admission (53.3 % vs. 16.7 %; P = 0.003). Multivariate analysis showed neutropenia, anemia and thrombocytopenia as risk factors for premature delivery and admission to NICU. Anemia was independently associated with low birth weight (OR 0.94, 95 % CI 0.9-0.98, P = 0.01). CONCLUSIONS: Neonatal complications such as premature delivery, low birth weight and NICU admission are more common in pregnant women with AA. Newborn babies' s hematopoietic system did not appear to have been affected. Maintaining a certain level of neutrophils, hemoglobin, and platelets in the mother can improve newborn outcomes.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Increasing Planting Density and Reducing N Application Improves Yield and Grain Filling at Two Sowing Dates in Double-Cropping Rice Systems.

Grain filling plays an important role in achieving high grain yield. Manipulating planting densities is recognized as a viable approach to compensate for the reduced yield caused by nitrogen reduction. Understanding the effects of nitrogen fertilization and planting density on superior and inferior grain filling is crucial to ensure grain security. Hence, double-cropping paddy field trials were conducted to investigate the effect of three nitrogen levels (N1, conventional nitrogen application; N2, 10% nitrogen reduction; N3, 20% nitrogen reduction) and three planting densities (D1, conventional planting density; D2, 20% density increase; D3, 40% density increase) on grain yield, yield formation, and grain-filling characteristics at two sowing dates (S1, a conventional sowing date, and S2, a date postponed by ten days) in 2019-2020. The results revealed that the annual yield of S1 was 8.5-14% higher than that of S2. Reducing nitrogen from N2 to N3 decreased the annual yield by 2.8-7.6%, but increasing planting densities from D1 to D3 significantly improved yield, by 6.2-19.4%. Furthermore, N2D3 had the highest yield, which was 8.7-23.8% higher than the plants that had received the other treatments. The rice yield increase was attributed to higher numbers of panicles per m2 and spikelets per panicle on the primary branches, influenced by superior grain filling. Increasing planting density and reducing nitrogen application significantly affected grain-filling weight, with the 40% density increase significantly facilitating superior and inferior grain filling with the same nitrogen level. Increasing density can improve superior grains while reducing nitrogen will decrease superior grains. These results suggest that N2D3 is an optimal strategy to increase yield and grain filling for double-cropping rice grown under two sowing-date conditions.

Noncoplanar Volumetric Modulated Arc Therapy for Hepatocellular Carcinoma Based on a Cage-Like Radiotherapy System: A Simulation Study.

BACKGROUND: The incorporation of noncoplanar beam arrangements has been proposed in liver radiotherapy modalities, which can reduce the dose in normal tissues compared to coplanar techniques. Noncoplanar radiotherapy techniques for hepatocellular carcinoma treatment based on the Linac design have a limited effective arc angle to avoid collisions. PURPOSE: To propose a novel noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system and investigate its performance in hepatocellular carcinoma patients. METHODS: The computed tomography was deflected 90° to meet the structure of a cage-like radiotherapy system and design the noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan in the Pinnacle3 planning system. An noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan was customized for each of 10 included hepatocellular carcinoma patients, with 6 dual arcs ranging from -30° to 30°. Six couch angles were set with an interval of 36° and distributed along with the longest diameter of planning target volume. The dosimetric parameters of noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan were compared with the noncoplanar volumetric modulated arc therapy and volumetric modulated arc therapy plan. RESULTS: The 3 radiotherapy techniques regarding planning target volume were statistically different for D98%, D2%, conformity index, and homogeneity index with χ2 = 9.692, 14.600, 8.600, and 12.600, and P = .008, .001, .014, and .002, respectively. Further multiple comparisons revealed that noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system significantly reduced the mean dose (P = .005) and V5 (P = .005) of the normal liver, the mean dose (P = .005) of the stomach, and V30 (P = .028) of the lung compared to noncoplanar volumetric modulated arc therapy. Noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system significantly reduced the mean dose (P = .005) and V5 (P = .005) of the normal liver, the mean dose (P = .017) of the spinal cord, V50 (P = .043) of the duodenum, the maximum dose (P = .007) of the esophagus, and V30 (P = .047) of the whole lung compared to volumetric modulated arc therapy. The results indicate that noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system protects the normal liver, stomach, and lung better than noncoplanar volumetric modulated arc therapy and protects the normal liver, spinal cord, duodenum, esophagus, and lung better than volumetric modulated arc therapy. CONCLUSIONS: The noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system technique with the arrangement of noncoplanar arcs provided optimal dosimetric gains compared with noncoplanar volumetric modulated arc therapy and volumetric modulated arc therapy, except for the heart. Noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system should be considered in more clinically challenging cases.

Assessment of delivered dose in prostate cancer patients treated with ultra-hypofractionated radiotherapy on 1.5-Tesla MR-Linac.

Objective: To quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac. Materials and methods: Seventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. Results: Overall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%-17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. Conclusions: This 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

[Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement].

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

Neonatal outcomes in pregnant women with pulmonary arterial hypertension associated with heart disease.

BACKGROUND: As an increasing number of women with pulmonary arterial hypertension (PAH) choose to become pregnant, outcomes in newborns have become a priority. The main purpose of this study was to compare the neonatal outcomes in pregnant women with PAH associated with heart disease. METHODS: A single-center retrospective study was performed. Pregnancy with heart disease is divided into three groups: no PAH, mild PAH and severe PAH. Neonatal outcomes of pregnant women were compared among groups. Meanwhile, multivariable analyses were used to investigate the association between maternal PAH and adverse neonatal events. RESULTS: A total of 127 pregnant women with heart disease were enrolled. Of these, 82 (64.6%) had no PAH, 19 (15%) had mild PAH and 26 (20.4%) had severe PAH. The offspring of women with severe PAH had a higher risk of preterm delivery, low birth weight, neonatal respiratory distress syndrome (NRDS), neonatal intensive care unit (NICU) admission and recurrence of congenital heart disease (CHD). Compared to the women without PAH, only the risk of preterm delivery (32-36 weeks) and NICU admission were slightly higher in mothers with mild PAH; other neonatal events were similar. Multivariate regression analyses showed that the risk of preterm delivery (<37 weeks) increased with the increasing severity of maternal PAH, with an OR of 3.1 (95% CI, 1.1-8.8) for mild and 21.9 (95%CI, 4.8-99.4) for severe PAH. The same pattern was observed for NICU admission. Mothers with severe PAH were independently associated with low birth weight (OR 13, 95%CI 4.3-39, P < 0.001), NRDS (OR 17.9, 95%CI 5.5-58.9, P < 0.001) and recurrence of CHD (OR 4.47, 95%CI 1.7-11.6, P = 0.002). CONCLUSION: Pregnancy in women with severe PAH can significantly increase the risks of neonatal events. While neonatal outcomes in pregnant women with mild PAH were considered optimistic in the present study, a multidisciplinary management of PAH in pregnancy would be necessary to have consistently good outcomes.

ARL9 is upregulated and serves as a biomarker for a poor prognosis in colon adenocarcinoma.

BACKGROUND: ARL9 is a newly identified member of the ARF family, and the clinical significance of ARL9 in colon adenocarcinoma is unknown. In this study, we aimed to explore the expression of ARL9 mRNA in colon adenocarcinoma, and its effect on the prognosis of patients with colon adenocarcinoma. METHODS: We investigated the differential expression of ARL9 between colon adenocarcinoma tissue and adjacent tissues through a bioinformatics analysis using The Cancer Genome Atlas (TCGA) database. The correlation between clinical characteristics and the mRNA expression level of ARL9 were analyzed. A survival analysis and a Cox regression analysis were used to determine the prognostic significance of ARL9. Finally, we conducted a gene set enrichment analysis (GSEA) to explore the ARL9 signaling pathways involved in the development of colon adenocarcinoma. The effect of the expression of ARL9 on the proliferation and migration of colon adenocarcinoma was analyzed by the CCK8 method and a cell scratch test, respectively. RESULTS: The mRNA expression of ARL9 in colon adenocarcinoma tissues was higher in comparison to the level in normal adjacent tissues (P < 0.05). The mRNA expression of ARL9 was not related to sex, tumor stage, T stage, N stage, M stage, but to age. The 5-year survival rate of colon adenocarcinoma patients with high ARL9 mRNA expression levels was significantly lower than that of patients with low ARL9 mRNA expression levels (P < 0.05). Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. After knocking down ARL9, the proliferation and migration abilities of colon adenocarcinoma cells were decreased (P < 0.01). CONCLUSION: The mRNA expression of ARL9 is upregulated in colon adenocarcinoma, and higher mRNA expression levels are associated with a poor prognosis. Knocking down ARL9 can reduce the proliferation and migration of colon adenocarcinoma cells. ARL9 mRNA can be used as a prognostic biomarker in patients with colon adenocarcinoma.

Neonatal Outcomes in Pregnant Women With Repaired and Unrepaired Congenital Heart Disease in Zhejiang, China.

OBJECTIVES: To compare the neonatal outcomes in pregnant women with repaired vs unrepaired congenital heart disease (CHD). METHODS: Data on pregnant women with CHD was retrieved from our hospital records for the duration April, 2014 to December, 2021. Pregnant women with CHD were divided into two groups: simple CHD and moderate-to-complex CHD. RESULTS: In simple CHD group, neonatal outcomes were similar in pregnant women with repaired and unrepaired CHD. By contrast, in moderate-to-complex CHD group, the offspring of women with unrepaired CHD had lower gestational age [mean (SD) 34.3 (2.7) vs 36.8 (2.1) week; P=0.016] and lower birth weight [mean (SD) 2126.8 (711.9) vs 2720 (645.7); P=0.037] than those with repaired CHD. Infants of women with unrepaired moderate-to-complex CHD had a higher risk of premature delivery (87.5% vs 45.5%, P=0.013), low birth weight (81.3% vs 36.4%, P=0.04) and neonatal intensive care unit (NICU) admission (68.8% vs 27.3%, P=0.034). CONCLUSION: Surgical repair before pregnancy in women with moderate-to-complex CHD significantly minimized the risks of neonatal complications.

PVECs-Derived Exosomal microRNAs Regulate PASMCs via FoxM1 Signaling in IUGR-induced Pulmonary Hypertension.

Background Intrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes. Methods and Results IUGR-induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs. Exosomes were isolated from PVEC-derived medium, and a microRNA (miRNA) screening was proceeded to identify effects of IUGR on small RNAs enclosed within exosomes. Dual-Luciferase assay was performed to validate the predicted binding sites of miRNAs on FoxM1 3' untranslated region. FoxM1 inhibitor thiostrepton was used in IUGR-induced PH rats. In this study, we found that FoxM1 expression was remarkably increased in IUGR-induced PH, and PASMCs were regulated by PVECs through FoxM1 signaling in a non-contact way. An miRNA screening showed that miR-214-3p, miR-326-3p, and miR-125b-2-3p were downregulated in PVEC-derived exosomes of the IUGR group, which were associated with overexpression of FoxM1 and more significant proliferation and migration of PASMCs. Dual-Luciferase assay demonstrated that the 3 miRNAs directly targeted FoxM1 3' untranslated region. FoxM1 inhibition blocked the PVECs-PASMCs crosstalk and reversed the abnormal functions of PASMCs. In vivo, treatment with thiostrepton significantly reduced the severity of PH. Conclusions Transmission of exosomal miRNAs from PVECs regulated the functions of PASMCs via FoxM1 signaling, and FoxM1 may serve as a potential therapeutic target in IUGR-induced PH.

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Ecosystem service (ES) bundle is a combination of various ecosystem services, serving as an indicator for the trade-off or synergy relationship among ecosystem services. Identifying the trade-off and synergy within ecosystem service bundles is helpful for realizing regional management and policymaking at the ES-bundle level. In this study, based on the InVEST model, the spatial composition, trade-off, and synergy of ES bundles, and their influencing factors were clarified using correlation analysis, cluster analysis, principal component analysis, and redundancy analysis. The results showed that the ESs in the Ziwuling Region (ZWLR) were generally improved from 2000 to 2017. The high-value area of soil conservation was concentrated in the northern part of the ZWLR, whereas other high-value areas of ESs were concentrated in the central and southern parts. According to the results of the cluster analysis, the ZWLR could be divided into four ES-bundles at pixel level. There was a strong tradeoff between water yield service and soil conservation in the core protected bundle, and a strong tradeoff between habitat quality, water yield service and food production in grain production bundle. The relationship between ESs in ecologi-cal transition bundle and ecologically fragile bundle was dominated by synergetic relationship. The ESs were affec-ted by both natural conditions and human activities. Vegetation cover, precipitation, and elevation had positive effects on the ESs, while temperature, the proportion of construction land, and population density had negative effects.