[Screening and functional analysis of differentially expressed long non-coding RNA in the liver of mice infected with Schistosoma japonicum during the chronic pathogenic stage].

OBJECTIVE: To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with Schistosoma japonicum during the chronic pathogenic stage and identify their functions, so as to provide insights into unravelling the role of lncRNAs in S. japonicum infection-induced liver disorders. METHODS: Twenty 6-week-old C57BL/6 mice were randomly divided into two groups, of 10 animals each group. Each mouse in the experimental group was infected with (15 ± 2) S. japonicum cercariae via the abdomen for modeling chronic S. japonicum infection in mice, and distilled water served as controls. All mice were sacrificed 70 days post-infection, and mouse liver specimens were sampled for RNA extraction and library construction. All libraries were sequenced on the Illumina NovaSeq 6000 sequencing platform. Data cleaning was performed using the fastp software, and reference genome alignment and gene expression (FPKM) calculation were performed using the HISAT2 software. Potential lncRNA sequences were predicted using the software CNIC, CPC, Pfam, and PLEK, and potential lncRNAs were screened. Differentially expressed lncRNAs were screened with the DESeq2 software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify biological processes and metabolic pathways involved in target genes of differentially expressed lncRNAs. RESULTS: A total of 333 potential lncRNAs were screened, and 67 were identified as differentially expressed lncRNAs, including 49 up-regulated and 18 down-regulated lncRNAs. A total of 53 target genes were predicted for differentially expressed lncRNAs. GO enrichment analysis showed that these target genes were mainly enriched in biological process and molecular function, among which Sema7a, Arrb1, and Ccl21b genes may be hub target genes for positive regulation of extracellular regulated protein kinase 1 (ERK1) and ERK2 cascades and may participate in the regulation of collagen expression. KEGG enrichment analysis showed that the target genes of differentially expressed lncRNAs were mainly enriched in cytokine-cytokine receptor interaction, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear factor kappa-B (NF-κB) signaling pathway. CONCLUSIONS: This study identifies differentially expressed lncRNAs and functional enrichment of their target genes in the liver of mice during the chronic pathogenic stage of S. japonicum infection. Up-regulated lncRNAs may affect biological processes of ERK1/2 cascades and chemokine signaling pathways via target genes Sema7a, Arrb1, and Ccl21b, thereby affecting collagen expression and inflammatory signal pathways, ultimately affecting the development of liver disorders.

Involvement of PD-1+CD4+ T cells in the development of traumatic tracheal stenosis by regulating the IL-17/STAT3 pathway.

Studies have highlighted an upregulation of PD-1 expression in CD4+ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-ß1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1+CD4+ T cells, IL-17A, and TGF-ß1 in the TS patients (n = 10). The cellular model used CD4+ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vitro (n = 5) and in vivo (n = 6) showed decreased expression of TGF-ß1 and IL-17A in CD4+ T cells, decreased collagen I synthesis in vitro, and reduced tractal fibrosis in vivo. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1+CD4+ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.

[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

[Distribution characteristics of emerging and reemerging Oncomelania hupensis in China from 2015 to 2021].

OBJECTIVE: To analyze the distribution characteristics of emerging and reemerging Oncomelania hupensis snails after the criteria for transmission control of schistosomiasis were achieved in China, so as to provide insights into assessment of schistosomiasis transmission risk and formulation of snail control strategies during the elimination phase. METHODS: O. hupensis survey data in China from 2015 to 2021 were collected from the National Schistosomiasis Pevention and Control Information Management System, and the distribution characteristics of emerging and reemerging O. hupensis snails were descriptively analyzed. RESULTS: Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with relatively larger areas with emerging and reemerging O. hupensis snail habitats in 2016 and 2021, and relatively higher numbers of counties (districts) where emerging and reemerging O. hupensis snails were detected in 2016 and 2021. A total of 4 586.30 hm2 of emerging O. hupensis snail habitats were found in 10 schistosomiasis-endemic provinces of China (except Fujian and Yunnan Provinces) from 2015 to 2021, with 96.80% in Anhui, Hunan and Hubei provinces, where marshland and lake endemic foci were predominant. A total of 21 023.90 hm2 of reemerging O. hupensis snail habitats were found in 12 schistosomiasis-endemic provinces of China from 2015 to 2021, with 97.67% in six provinces of Hubei, Sichuan, Jiangxi, Jiangsu, Yunnan and Anhui, where marshland and lake and hilly endemic regions were predominant. Emerging snail habitats were found in 15.08% of all schistosomiasisendemic counties (districts) in China from 2015 to 2021, and 78.75% of all emerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of emerging snail habitats found in Lixian County, Hunan Province (645.00 hm2). Reemerging snail habitats were found in 47.67% of all schistosomiasis-endemic counties (districts) in China from 2015 to 2021, and 43.29% of all reemerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of reemerging snail habitats found in Weishan Li and Hui Autonomous County of Hunan Province (1 579.70 hm2). CONCLUSIONS: Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with much larger areas of reemerging snail habitats than emerging snail habitats, and larger numbers of schistosomiasis-endemic provinces and counties (districts) with reemerging snails were found that those of provinces and counties (districts) with emerging snails. Specific snail control interventions are required tailored to the causes of emerging and reemerging snail habitats. Both emergence and reemergence of O. hupensis snails should be paid attention to in marshland and lake endemic areas, and Guangxi Zhuang Autonomous Region, Shanghai Municipality and Zhejiang Province where schistosomiasis had been eliminated, and reemergence of O. hupensis snails should be given a high priority in hilly areas. In addition, monitoring of O. hupensis snails should be reinforced in snail-free areas after flooding.

The effect of the enhanced recovery after surgery protocol and the reduced use of opioids on postoperative outcomes in elderly patients with colorectal cancer.

OBJECTIVE: The study aimed to assess the impact of the enhanced recovery after surgery (ERAS) pathways and the reduced use of opioids on postoperative outcomes in elderly colorectal cancer (CRC) patients who underwent laparoscopic surgery under general anesthesia (GA). PATIENTS AND METHODS: Clinical data from 99 elderly patients who underwent laparoscopic CRC surgery in the First Affiliated Hospital of Hebei North University from April 2021 to April 2023 were retrospectively analyzed and grouped based on the method of pain control measures received. Of 99 patients, 51 received conventional doses of opioid drugs (conventional group), and 48 patients were treated with reduced doses of opioids based on the principles of ERAS (low-dose group). Perioperative characteristics, postoperative pain level, cognitive function, serum biochemical index levels, and adverse reactions were compared between the two groups. RESULTS: The first exhaust time, defecation time, and bedtime activity time of the low-dose group were compared to the conventional group (p<0.05). On the first day after the surgery, the mini-mental state examination (MMSE) score of the low-dose group was higher than the conventional group (p<0.05). After the surgery, the levels of serum brain-derived neurotrophic factor (BDNF) decreased in both groups, while the levels of neuron-specific enolase (NSE) and 5-hydroxytryptamine (5-HT) increased. However, compared to the conventional group, the low-dose group had higher levels of BDNF and lower levels of NSE and 5-HT (p<0.05). The incidence of adverse reactions in the low-dose group was lower than that in the conventional group (p<0.05). CONCLUSIONS: ERAS protocol and the reduced use of opioid drugs in CRC patients who underwent surgery under GA is associated with an analgesic effect that is comparable to that of conventional opioid use. Reduced dosage of opioid drugs lessened cognitive impairment and lowered the incidence of adverse reactions in surgical patients with CRC.

Utilizing machine learning techniques to predict the blood-brain barrier permeability of compounds detected using LCQTOF-MS in Malaysian Kelulut honey.

Current in silico modelling techniques, such as molecular dynamics, typically focus on compounds with the highest concentration from chromatographic analyses for bioactivity screening. Consequently, they reduce the need for labour-intensive in vitro studies but limit the utilization of extensive chromatographic data and molecular diversity for compound classification. Compound permeability across the blood-brain barrier (BBB) is a key concern in central nervous system (CNS) drug development, and this limitation can be addressed by applying cheminformatics with codeless machine learning (ML). Among the four models developed in this study, the Random Forest (RF) algorithm with the most robust performance in both internal and external validation was selected for model construction, with an accuracy (ACC) of 87.5% and 86.9% and area under the curve (AUC) of 0.907 and 0.726, respectively. The RF model was deployed to classify 285 compounds detected using liquid chromatography quadrupole time-of-flight mass spectrometry (LCQTOF-MS) in Kelulut honey; of which, 140 compounds were screened with 94 descriptors. Seventeen compounds were predicted to permeate the BBB, revealing their potential as drugs for treating neurodegenerative diseases. Our results highlight the importance of employing ML pattern recognition to identify compounds with neuroprotective potential from the entire pool of chromatographic data.

[The clinical characteristics of Parkinson's disease patients with concomitant periodic limb movements in sleep].

The current study aimed to investigate the clinical characteristics of Parkinson's disease (PD) patients with concomitant periodic limb movements in sleep (PLMS). The clinical data of 36 PD patients who underwent polysomnography (PSG) in Beijing Tiantan Hospital from October 2018 to July 2022 were collected. Unified Parkinson's Disease Rating Scale 3.0 and Hoehn & Yahr (H-Y) stage were used to evaluate the disease severity. Patients were divided into two groups: the PLMS+group periodic limb movements in sleep index [(PLMSI)≥15 times/h] and the PLMS-group (PLMSI<15 times/h), using the PLMSI 15 times/h as the cut-off value. The clinical characteristics between the two groups were compared. There were 15 patients (42%) in the PLMS+group and 21 patients (58%) in the PLMS-group, among which 12 patients (12/15) in the PLMS+group and 9 patients (42.9%) in the PLMS-group had rapid eye movement sleep behavior disorder (RBD). The rate of RBD in PLMS+group was higher than that in PLMS-group (P<0.05). There was statistically significant difference in the blood folate level between the PLMS-group and PLMS+group [6.20 (5.14, 11.70) ng/ml vs 4.41 (3.07, 5.64) ng/ml] (P<0.01). Folate deficiency was more common in the PLMS+group, while no statistically significant differences were found in homocysteine and ferritin levels (both P>0.05). Four patients in the PLMS+group had falling experience, while 14.3% (3/21) patients in the PLMS-group had falling experience. Patients in the PLMS+group were more likely to fall. The PLMS+group had higher arousal index according to PSG [PLMS-group: 11.90 (9.10, 15.80) times/h; PLMS+group: 21.50 (19.35, 29.90) times/h] (P<0.05). No statistically significant differences in other sleep parameters were detected between the two groups (all P>0.05). Meanwhile, the apnea-hypopnea index (AHI) in both groups was higher than normal (<5 times/h), of which the PLMS-group was 9.80 (4.70, 22.20) times/h and the PLMS+group was 8.20 (1.70, 11.15) times/h, indicating that PD patients were more likely to experience sleep apnea and hypopnea. PD patients with PLMS had lower folate level, higher risk for falls, higher sleep arousal index, more sleep fragmentation, and higher prevalence of RBD.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage â ¢c squamous cervical cancer].

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

[Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma].

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

Causal roles of daytime sleepiness in cardiometabolic diseases and osteoporosis.

OBJECTIVE: Daytime sleepiness has some association with cardiometabolic diseases and osteoporosis, but it is unknown whether their relationship is causal. This two-sample Mendelian randomization (MR) study aims to explore their causal relationship. MATERIALS AND METHODS: We included the largest genome-wide association studies (GWASs) associated with daytime sleepiness, cardiometabolic diseases and osteoporosis. 34 single nucleotide polymorphisms (SNPs) were used as the instrumental variables of daytime sleepiness. RESULTS: Genetic predisposition to excessive daytime sleepiness was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.610, 95% confidence interval [CI]: 0.128 to 1.093, standard error [SE]: 0.246, p-value=0.013) and may increase the incidence of type 2 diabetes (beta-estimate: 0.614, 95% CI: 0.009 to 1.219, SE: 0.309, p-value=0.047). We found no causal influence of daytime sleepiness on heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage, forearm bone mineral density (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD). CONCLUSIONS: This study suggested that excessive daytime sleepiness was causally associated with increased risk of coronary artery disease, which may benefit to prevent this disease.

Effects of kisspeptin-10 on the reproductive performance of sows in a fixed-time artificial insemination programme.

Kisspeptin (KP) is a major positive regulator of the hypothalamo-pituitary-gonadal axis and affects female reproductive cyclicity in mammals. It offers an attractive alternative strategy to control reproduction in fixed-time artificial insemination (FTAI) protocols. We aimed to evaluate the effects of different doses of kisspeptin-10 (KP-10) on sow reproductive performance in FTAI protocols. One hundred ninety-eight weaned sows were divided into three groups at random. A FTAI-GnRH group of sows (n = 98) received 100 µg (2 mL) gonadotropin-releasing hormone (GnRH; gonadorelin) by intramuscular injection at 96 h after weaning (t = 0 h); FTAI-KPL (KPL: low-dose KP-10, n = 50), and FTAI-KPH groups of sows (KPH: high-dose KP-10, n = 50) received 0.5 or 1 mg KP-10 (2 mL) respectively at 96 h after weaning. Sows were checked twice daily for oestrus. Ultrasonographic evaluations were performed to determine the follicular diameter and time of ovulation; blood samples were collected immediately before injection (t0 = 0 min) and at 15, 30, 45, 60, 75, 90 min, 24 and 48 h postinjection. Sows were inseminated at 112 and 132 h after weaning. The oestrus rates (96 vs 92%; 96 vs 88%) and weaning-to-oestrus intervals (98.9 vs 98.6 h; 98.9 vs 97.1 h) were not affected by treatment, but oestrus in the FTAI-KPL group was significantly longer than in the FTAI-GnRH group (38.7 vs 30.0 h; P < 0.05). The peak LH concentrations were 1.29 times greater than at t0 = 0 in the FTAI-GnRH group, and 1.45 and 1.44 times greater than at t0 = 0 in the FTAI-KPL and FTAI-KPH groups, respectively. Follicular diameters and pregnancy rates (86 vs 88%, 86 vs 80%, respectively) did not differ between the treatments. Moreover, the total numbers of piglets born and those born alive did not differ among the three groups. These findings suggested that 0.5 mg KP-10 given at 96 h after weaning could be used in FTAI programmes to manage batch farrowing in sows.

Saturated hydraulic conductivity of compacted steel slag-bentonite mixtures--A potential hydraulic barrier material of landfill cover.

The feasibility of using steel slag and bentonite mixtures to construct the hydraulic barrier of a landfill cover was explored in the present study. Fine-grained steel slag (SS; particle diameter < 1 mm) and sodium-activated calcium bentonite (SACB) were used to prepare compacted specimens, and the saturated hydraulic conductivity (ks) was measured using a flexible-wall permeameter. Influential factors including SACB content (BC), SS gradation, water-washing treatment of SS and compaction water content (ωcomp) were investigated. The hydraulic conductivity results were interpreted in microscopic scale through mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). It was found that when BC was below 10%, the ks value of the specimens prepared with well graded SS was about one order of magnitude lower than that of the specimens prepared with poorly graded SS. This was due to less macropores caused by better SS gradation. Yet, the effects of SS gradation on ks diminished as BC further increased to 15%, suggesting the dominant role of BC on ks at high BC. Water-washing treatment of SS helped reduce ks significantly to 1.2 × 10-10 m/s at BC of 10%, owing to less multivalent cations and hence lower osmotic swelling reduction caused by cations. Controlling ωcomp 1-2% wetter than the optimum water content (ωopt) also helped reduce ks significantly, owing to the reduction of macropores. Accordingly, it is suggested to use well-graded SS mixed with 10% SACB and then compact at ωcomp slightly wetter than ωopt to the degree of compaction greater than 90% in engineering practice.

[Effect of RBP2 gene silencing on proliferation, migration and invasion of ovarian epithelial cancer SKOV3/DDP cells and its mechanism].

Objective: To explore the effect of down-regulation of retinol binding protein 2 (RBP2) expression on the biological characteristics of ovarian cancer cells and its mechanism. Methods: Knockdown of RBP2 and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP-RBP2i was established, the negative control group and blank control group were also set. Cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect cell apoptosis, scratch test and Transwell invasion test were used to detect cell migration and invasion ability, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of molecular markers related to epithelial-mesenchymal transition (EMT). The effect of RBP2 on the growth of ovarian cancer was verified through experiment of transplanted tumors in nude mice, and the relationships between RBP2 expression and tumor metastasis and patient prognosis were analyzed using the clinical data of ovarian cancer in TCGA database. Results: After down-regulating the expression of RBP2, the proliferation ability of SKOV3/DDP cell was significantly reduced. On the fifth day, the proliferation activities of SKOV3/DDP-RBP2i group, negative control group and blank control group were (56.67±4.16)%, (84.67±3.51) and (87.00±4.00)% respectively, with statistically significant difference (P<0.001). The apoptosis rate of SKOV3/DDP-RBP2i group was (14.19±1.50)%, higher than (8.77±0.75)% of the negative control group and (7.48±0.52)% of the blank control group (P<0.001). The number of invasive cells of SKOV3/DDP-RBP2i group was (55.20±2.39), lower than (82.60±5.18) and (80.80±7.26) of the negative control group and the blank control group, respectively (P<0.001). The scratch healing rate of SKOV3/DDP-RBP2i group was (28.47±2.72)%, lower than (50.58±4.06)% and (48.92±4.63)% of the negative control group and the blank control group, respectively (P<0.001). The mRNA and protein expressions of E-cadherin in the SKOV3/DDP-RBP2i group were higher than those in the negative control group (P=0.015, P<0.001) and the blank control group (P=0.006, P<0.001). The mRNA and protein expression of N-cadherin in SKOV3/DDP-RBP2i group were lower than those in the negative control group (P=0.012, P<0.001) and the blank control group (P=0.005, P<0.001). The mRNA and protein expressions of vimentin in SKOV3/DDP-RBP2i group were also lower than those in the negative control group (P=0.016, P=0.001) and the blank control group (P=0.011, P=0.001). Five weeks after the cells inoculated into the nude mice, the tumor volume of SKOV3/DDP-RBP2i group, negative control group and blank control group were statistically significant different. The tumor volume of SKOV3/DDP-RBP2i group was smaller than those of negative control group and blank control group (P=0.001). Bioinformatics analysis showed that the expression of RBP2 in patients with metastatic ovarian cancer was higher than that without metastasis (P=0.043), and the median overall survival of ovarian cancer patients with high RBP2 expression was 41 months, shorter than 69 months of low RBP2 expression patients (P<0.001). Conclusion: Downregulation of the expression of RBP2 in SKOV3/DDP cells can inhibit cell migration and invasion, and the mechanism may be related to the inhibition of EMT.

[Initial clinical experience of left bundle branch pacing after transcatheter aortic valve implantation].

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.

Nitrogen-plasma doping of carbon film for a high-quality layered Si/C composite anode.

The effect of the chemical component and microstructure, not to mention their facile modification, of the coating/wrapping carbon layer on the electrochemical performance of the Si/C composite anode in lithium ion batteries (LIBs) hasn't been actively explored although Si/C has been recognized as one of the most promising route for the high energy density LIBs. Herein we propose a novel nitrogen-plasma doping route to modify the top carbon film in an elaborately constructed layered Si/C composite anode. The electrochemical performance, e.g., the initial coulombic efficiency (CE), cycle stability and specific capacity of the composite anode is drastically improved by this plasma processing due to the increased kinetics of lithium ions. By means of the appropriate adjustment of the N doping ratio and N chemical configuration in the carbon layer through a N2/H2 plasma processing, the lithium diffusion rate in the composite anode was memorably increased as the pseudocapacitance effects promoted. The optimized Si/C composite exhibits a high capacity of 1120.7 mA h g-1 and an initial CE of 80.8% at the current of 2 A g-1 after a long cycle of 1500, increasing by ~40% of specific capacity and ~29% of the initial CE.

A synonymous mutation in IGF-1 impacts the transcription and translation process of gene expression.

Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wild-type (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes.

A comparison of the reproductive performance in primiparous sows following two timed artificial insemination protocols.

Timed artificial insemination (TAI) is an efficient reproductive technology in batch farrowing production that aids management in pig farms. However, the effect of TAI on the reproduction performance is still controversial. This study aimed to evaluate the effects of two TAI protocols on the reproductive performance of primiparous sows. A total of 332 weaned sows were randomly allocated into three treatments. Sows assigned to Control (n = 110) were untreated and inseminated on each day in oestrus after weaning. Sows assigned to eG-TAI (n = 112) received equine chorionic gonadotropin (eCG) 24 h after weaning and gonadotropin-releasing hormone (Gonadorelin: GnRH) at oestrus, and were inseminated at 8 and 32 h later if oestrus at 0800, or 16 and 40 h later if oestrus at 1600. Sows assigned to 2e-TAI (n = 110) received eCG and GnRH 24 h and 96 h after weaning, respectively, and were inseminated 16 and 40 h after GnRH administration. Sows showing oestrus at GnRH administration or 64 h after were inseminated immediately, for a total of three inseminations. Ultrasonographic evaluations were performed to determine the follicular diameter and time of ovulation. Most sows in the 2e-TAI and eG-TAI groups ovulated 0-48 h after the GnRH injection. Our results indicated that oestrus rate within seven days after weaning in the experimental groups was higher, and weaning-to-oestrus interval was shorter than in the control group (99.3 h vs 113.5 h, P < 0.05). The breeding and farrowing rates in the experimental groups were significantly higher than in the control group (P < 0.05), while the numbers of total born, live-born and stillborn were not different among the three groups (Control: 12.7, 11.6 and 1.1; 2e-TAI: 12.4, 11.3 and 1.0; eG-TAI: 12.0, 11.4 and 0.4, respectively). These results indicated that TAI could ensure a high farrowing rate in primiparous sows under batch farrowing management.

[Effectiveness of influenza vaccination for school-age children in preventing school absenteeism in Shenzhen: an empirical study].

Objective: To assess the impact of vaccination at school and influenza vaccination rates among school-age children on school absenteeism in Shenzhen. Methods: The study subjects were primary school students in Shenzhen. School absenteeism panel database from December 2017 to June 2020 of 286 primary schools in Shenzhen was merged with vaccination rates and organizational patterns (i.e., vaccination at school vs. non-school) data of 9 districts in Shenzhen after influenza vaccination for children. The outcome was the number of school absenteeism. The treatment and control groups were distinguished by organizational patterns and district vaccination rates. Difference-in-Difference (DiD) Poisson regressions were used to analyze the effectiveness of vaccination at school and higher vaccination rates. Besides, a robustness test was performed on the regression results. Results: Poisson regression analysis and robustness test of regression results showed that vaccination at school and higher vaccination rates effectively reduced the risk of school absenteeism, with effectiveness against absenteeism of 32.6% (95%CI: 17.0%-45.3%, P<0.01) and 53.0% (95%CI: 42.1%-61.8%, P<0.01), respectively. Conclusion: A free influenza vaccination program for school-age children in Shenzhen and prioritizing school-based vaccination may be an effective measure to reduce the risk of school absenteeism.

[Transcranial sonographic characteristics of Parkinson's disease with symptoms of restless legs syndrome].

Objective: To evaluate the transcranial sonographic characteristics in patients with Parkinson's disease (PD) with symptoms of restless legs syndrome (RLS). Methods: Patients with diagnosis of definite PD from the Second Affiliated Hospital of Soochow University and 3 other participating hospitals between September 2018 and December 2019 were consecutively enrolled. Concurrent RLS symptoms were determined using Non-motor Symptoms Questionnaire. Transcranial sonography (TCS) and clinical assessments were performed during the same time and the related variables were compared between the two groups using t-test, non-parametric test, Chi-square test and Spearman correlation analysis, respectively. Results: Among 349 patients with PD, the prevalence of RLS symptoms was 22.6%. Compared to patients without RLS symptoms, those with RLS had longer disease duration (43.0 (24.0, 91.0) months vs 37.0 (20.0, 60.0) months, P<0.05) and higher Hoehn-Yahr stage (2.5 (2.0, 3.0) vs 2.0 (1.5, 2.5), P<0.01).TCS revealed that patients with RLS symptoms were more likely to have abnormality in the raphe nucleus (21.50% vs 7.78%, χ²=15.9, P<0.001) and increased third ventricle width ((6.22±1.97) mm vs (5.16±1.90) mm, P<0.001). No significant differences were found regarding parameters of substantia nigra. Conclusions: Concurrent RLS symptoms are common in PD patients. Abnormal echogenicity of raphe nucleus and increased third ventricle width could be characteristics of TCS in PD patients with RLS symptoms.