Long non-coding RNA PMS2L2 is down-regulated in osteoarthritis and inhibits chondrocyte proliferation by up-regulating miR-34a.

Long non-coding RNA (lncRNA) PMS2L2 has been reported to participate in endotoxin-induced inflammatory responses. As these types of responses can promote osteoarthritis (OA), it was of interest to ascertain if PMS2L2 may be involved in OA. To explore any potential participation of PMS2L2 in OA, synovial fluid was extracted from both OA patients and healthy controls (n = 62 each) and PMS2L2 expression of each sample determined by RT-qPCR. In addition, as miR-34a has a potential binding site on PMS2L2, hypothetical interactions between PMS2L2 and miR-34a in chondrocytes were analyzed by performing over-expression experiments. Furthermore, the role of PMS2L2 and miR-34a in the regulation of chondrocyte proliferation was analyzed using CCK-8 and BrdU assays. The results showed that PMS2L2 expression in OA patient synovial fluid was lower compared to that in control group fluid, and the extent of this reduction was related to disease stage. In in vitro studies, it was seen that endotoxin treatment of chondrocytes led to decreased PMS2L2 expression. It was found that PMS2L2 over-expression caused increased miR-34a expression in OA patient chondrocytes but not in cells from healthy controls. In contrast, miR-34a over-expression in either cell population did not affect PMS2L2 expression. Lastly, over-expression of both PMS2L2 and miR-34a led to inhibited chondrocyte proliferation. Of note, a combined over-expression of PMS2L2 and miR-34a resulted in stronger effects on proliferation compared to that from either single over-expression. Based on the findings that PMS2L2 is down-regulated during ongoing states of OA, and that changes in PMS2L2 expression can lead to increases in chondrocyte expression of miR-34a - resulting in inhibition of chondrocyte proliferation in OA. From these findings, one may conclude that finding means to regulate PMS2L2 could be a promising new target in the development of regimens for the treatment of OA.

Epidemiology of necrotizing enterocolitis in preterm infants in China: A multicenter cohort study from 2015 to 2018.

PURPOSE: To describe the current incidence, case-fatality rate and surgical treatment proportion of necrotizing enterocolitis (NEC) among preterm infants in China. METHODS: The study included all live neonates with <34 weeks gestational age (GA) admitted to 25 tertiary hospitals within 7 days of birth from 19 provinces in China between May 2015 and April 2018. NEC was defined as ≥stage II according to Bell's criteria. RESULTS: A total of 24,731 infants were included. The overall incidence of NEC was 3.3% and decreased with increasing GA and birth weight. The incidence of NEC was 4.8% in very preterm infants and 1.8% in infants born ≥32 weeks GA, respectively. The overall case-fatality rate of NEC was 9.5%, and the case-fatality rate was 7.0% among infants born ≥32 weeks GA. A total of 214 (27.9%) infants underwent surgery, and their overall case-fatality rate was 13.6%. Significant variation in the incidence of NEC existed among different centers (0.6-11.1%). CONCLUSIONS: The incidence and case-fatality rate of NEC are high in China, especially among infants with GA ≥32 weeks, and varies significantly among sites. A high proportion of NEC infants required surgical management, with an even higher case-fatality rate.

Exosomal miR-183-5p Shuttled by M2 Polarized Tumor-Associated Macrophage Promotes the Development of Colon Cancer via Targeting THEM4 Mediated PI3K/AKT and NF-κB Pathways.

BACKGROUND: Abnormal accumulation of macrophages in the colon cancer (CC) contribute to its progression. miR-183-5p has been confirmed as an oncogene in CC and this article explores the effect and mechanism of exosomal miR-183-5p enriched by M2-polarized tumor-associated macrophages (TAM) on CC cells. METHODS: The human macrophage THP1 was induced to M2 polarization through IL-4 and IL-13 treatment. Exosomes in THP1 were isolated through ultracentrifugation, and the miR-183-5p expression in macrophages and exosomes was verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miR-183-5p inhibitors and mimics were applied to down-regulate and upregulate miR-183-5p in macrophages, respectively. Meanwhile, CC cell lines LoVo and SW480 were treated with the macrophage conditioned medium and exosomes, respectively. CC cells' proliferation, invasion, and apoptosis were tested by the cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry (FCM), Transwell assay, and xenograft assay, respectively. The profiles of thioesterase superfamily member 4 (THEM4), Akt, and NF-κB were compared by Western blotting (WB). RESULTS: The miR-183-5p level in M2-TAM and M2-TAM-derived exosomes was significantly increased. Meanwhile, M2-TAM and M2-TAM-derived exosomes significantly facilitated CC cell proliferation and invasion and dampened apoptosis. Overexpression of miR-183-5p in M2-TAM aggravated M2-TAM-mediated promotive effects on CC cells, with down-regulating miR-183-5p reversed M2-TAM-mediated tumor-promotive effects. Mechanically, miR-183-5p targeted THEM4 and inhibited its mRNA and protein expression. Overexpressing THEM4 abated miR-183-5p-mediated carcinogenic effects and inactivates Akt and NF-κB pathways in CC cells. Overall, this article elaborated that exosomal miR-183-5p shuttled by M2-TAM mediated Akt/NF-κB pathway to accelerate CC progression through targeting THEM4.

Study of quickly separating water from tunneling slurry waste by combining vacuum with electro-osmosis.

Tunneling slurry waste causes multiple problems, including environmental pollution, and requires transportation and a large landfill space, and therefore, it is important to find a method that can quickly separate water from tunneling slurry waste for metro construction. This paper proposes a practical method to improve the effect of slurry waste separation by implementing five laboratory tests. The results of these tests reflect that vacuum combined electro-osmosis is a suitable and practical method for treating tunneling slurry waste. The water content after treatment by vacuum combined horizontal electric field electro-osmosis method is not only lower than that after other methods but also close to the liquid limit, which fully meets the requirements of engineering transportation. However, vacuum and filter press dewatering cannot give full play to the drainage effect when the slurry permeability coefficient is too low. This combined technique can improve water separation from the slurry and works well in engineering applications.

A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother's own milk for preterm infants in the NICU.

BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks' gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother's own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed. METHODS: Our prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks' gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks' corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks' corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors. DISCUSSION: Our double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants. TRIAL REGISTRATION: Chinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019; http://www.chictr.org.cn/showprojen.aspx?proj=34276.

[Delorme procedure for full-thickness rectal prolapse: a report of 25 cases].

OBJECTIVE: To evaluate the use of Delorme procedure for full-thickness rectal prolapse. METHODS: A series of 25 patients with full-thickness rectal prolapse were treated by Delorme procedure in four institutions between March 2005 and June 2010. The clinicopathological data were analyzed retrospectively. RESULTS: There were 9 males and 16 females. The mean age was 52(46-72) years old. All the procedures were successfully performed. There were no perioperative deaths. The mean operative time was 65(45-150) min. The intraoperative bleeding was 58(20-200) ml. The mean length of hospital stay was 8.5(5-14) days. Anastomosis dehiscence occurred in 1 patient at post-operative day 7 who was managed under anesthesia. Minor complications occurred in 8(32%) patients, including urinary retention(n=3), intractable pain(n=1), and bowel obstruction(n=4). The follow up time ranged from 2 to 6 years with a median of 3.5 years. Prolapse recurrence was observed in 1(4%) patient during the follow up. The remission rates of fecal incontinence, constipation, bleeding were 37.5%(6/16), 45.5%(5/11), and 15.4%(2/11), respectively. The Wexner incontinence score significantly decreased (median, 5.0 vs. 9.0, P<0.01). The resting pressure and maximum squeeze pressure increased significantly after surgery, while the initial volume and maximal tolerance volume decreased significantly(All P<0.01). CONCLUSIONS: Delorme procedure is safe and easy to perform. The anorectal function is improved after surgery. Therefore it should be considered the procedure of choice for rectal prolapsed.

Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge.

Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 microg of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49. With the short schedule a total of seven or six doses of 25 microg (lot #111) were administered on days 1, 2, 3, 14, 15, 16 and 30, or on 1, 2, 14, 15, 30, 31 and 32, respectively. Mice immunized orally with the long schedule, 50 microg of RT vaccine incorporated into poly-DL-lactide-co-glycolyde (DL-PLG) microspheres (MS) produced serum IgG, IgG2a and IgA ELISA antibodies. All mice immunized with RT in DL-PLG MS (RT-MS) were protected against a lethal ricin aerosol challenge. In contrast, with the same schedule and with the same dose, the aqueous vaccine (RT) failed to stimulate IgG, IgG2a and IgA antibodies, and these mice were not protected against an aerosol ricin toxin challenge. With the shorter immunization scheme, seven doses of 25 microg RT-MS stimulated a significant, though reduced, protection with the microencapsulated, but not with the aqueous vaccine. When the first and second 3-day cycles of the short immunization schedule was reduced to two doses, and the 3-day cycle was administered at the end of the schedule, neither RT-MS nor RT stimulated protection against the challenge. These results indicated that successful oral immunization with RT-MS depended on both the dose and the schedule, consisting of three consecutive days of administration in two cycles, 4 weeks apart. Altering this schedule and the dose, resulted in a reduced protection or no protection at all. Furthermore, under the conditions of this study, the advantage of the microencapsulated RT vaccine over the aqueous vaccine for effective oral immunization was well demonstrated.