Kikuchi disease: A case report about Sintilimab-induced Kikuchi histiocytic necrotizing lymphadenitis and literature review.

Immune checkpoint inhibitors have become one of the effective means of solid tumor treatment, among which anti-programmed death-1 (PD-1) antibodies are more maturely applied and can effectively inhibit tumor immune escape, thus enhancing the anti-tumor effect, but it can also lead to a series of immune-related adverse events (irAEs) in the process of clinical use. Here, we report a Patient with pancreatic solid pseudopapilloma treated with Sintilimab for the fifteenth cycles who developed chills, fever, and lymph node enlargement. Considering that the patient did not have infection, without history of autoimmune disease, we diagnosed the patient with Sintilimab-induced histiocytic necrotizing lymphadenitis (Kikuchi disease). The symptoms are alleviated after rapid use of glucocorticoids. Histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis) with anti-programmed death-1 (PD-1) antibody is a rare immune-related adverse events (irAEs).

[Construction and Optimization of CD19 Chimeric Antigen Receptor T Cells Derived from C57BL/6J Mice].

OBJECTIVE: To explore the stimulation conditions, optimal culture time and infection time of C57BL/6J mice CD3+ T cells in vitro, so as to improve the infection efficiency of CD19 chimeric antigen receptor T cells (mCD19 CAR-T). METHODS: Purified C57BL/6J mice CD3+ T cells were cultured in anti-CD3/CD28 coated, anti-CD3 coated+soluble anti-CD28 and anti-CD3 coated, respectively. The cells were stimulated in above three conditions for 12 h and 24 h, following with 24 h, 48 h and 72 h incubation and then the number of cell clones was recorded. C57BL/6J mice CD3+ T cells were stimulated for 12 h, 24 h, and 36 h under the above three conditions, then interleukin (IL)-2 (100 U/ml) was added. The number of cell clones was recorded under microscope at 24 h, 48 h, and 72 h of culture. After 24 h of stimulation, CD3+ T cells derived from C57BL/6J mice were infected with retrovirus for 48 h to establish mCD19 CAR-T cells, and the percentage of GFP+ CAR-T cells was detected by flow cytometry. RESULTS: The infection efficiency of mCD19 CAR-T cells derived from C57BL/6J mice was only 5.23% under the optimized conditions of mCD19 CAR-T cells derived from BALB/c mice. The number of clones of C57BL/6J mice CD3+ T cells was the highest in anti-CD3 coated+soluble anti-CD28 group after stimulated for 24 h and followed cultured for 48 h. After 24 hours of stimulation under the above conditions and 48 hours of culture with IL-2, the number of T cell proliferating clones in the anti-CD3 coated+soluble anti-CD28 group was significantly increased compared with the same group without IL-2, and the infection efficiency of CAR-T cells in this group reached 17.63%±4.17%. CONCLUSION: The optimal conditions for constructing CAR-T cells from C57BL/6J mice CD3+ T cells are different from those of BABL/c mice. T cells stimulated by anti-CD3 coated+soluble anti-CD28+IL-2 can obtain mCD19 CAR-T cells with the highest efficiency after retrovirus infection.

Drying Kinetics of Microwave-Assisted Drying of Leaching Residues from Hydrometallurgy of Zinc.

In the hydrometallurgical process of zinc production, the residue from the leaching stage is an important intermediate product and is treated in a Waelz kiln to recover valuable metals. To ensure optimal results during the Waelz kiln process, it is necessary to pre-treat the residues by drying them first due to their higher water content. This work studies the residue's drying process using microwave technology. The study results indicate that microwave technology better removes the residue's oxygen functional groups and moisture. The dehydration process's effective diffusion coefficient increases as the microwave's heating power, the initial moisture content, and the initial mass increase. The Page model is appropriate for imitating the drying process, and the activation energy of the drying process for the residues is -13.11217 g/W. These results indicate that microwave technology efficiently dries the residues from the leaching stage. Furthermore, this study provides a theoretical basis and experimental data for the industrial application of microwave drying.

The altering cellular components and function in tumor microenvironment during remissive and relapsed stages of anti-CD19 CAR T-cell treated lymphoma mice.

Anti-CD19 chimeric antigen receptor (CAR) T cells represent a highly promising strategy for B-cell malignancies. Despite the inspiring initial achievement, remission in a notable fraction of subjects is short-lived, and relapse remains a major challenge. Tumor microenvironment (TME) was proved to be aroused by CAR T cells; however, little is known about the dynamic characteristics of cellular components in TME especially during the different phases of disease after anti-CD19 CAR T-cell treatment. We took advantage of an immunocompetent model receiving syngeneic A20 lymphoma cells to dissect the changes in TME with or without CAR T-cell injection. We found that anti-CD19 CAR T-cell treatment attenuated the symptoms of lymphoma and significantly prolonged mice survival through eradicating systemic CD19+ cells. Increased myeloid subsets, including CD11c+ DCs and F4/80+ macrophages with higher MHC II and CD80 expression in bone marrow, spleen, and liver, were detected when mice reached remission after anti-CD19 CAR T treatment. Compared to mice without anti-CD19 CAR T administration, intrinsic T cells were triggered to produce more IFN-γ and TNF-α. However, some lymphoma mice relapsed by day 42 after therapy, which coincided with CAR T-cell recession, decreased myeloid cell activation and increased Treg cells. Elevated intrinsic T cells with high PD-1 and TIGIT exhaust signatures and attenuated cytotoxicity in TME were associated with the late-stage relapse of CAR T-cell treatment. In summary, the cellular compositions of TME as allies of CAR T cells may contribute to the anti-tumor efficacy at the initial stage, whereas anti-CD19 CAR T-cell disappearance and host response immunosuppression may work together to cause lymphoma relapse after an initial, near-complete elimination phase.

A Combination of Formic Acid and Monolaurin Attenuates Enterotoxigenic Escherichia coli Induced Intestinal Inflammation in Piglets by Inhibiting the NF-κB/MAPK Pathways with Modulation of Gut Microbiota.

This study determined the potential of formic acid plus monolaurin (FA + ML) as an alternative to antibiotics in diet when piglets are challenged with ETEC. Piglets fed the FA + ML diet had lower fecal score and rectal temperature after the ETEC challenge. In addition, FA + ML supplementation induced lower plasma TNF-α, IL-6, and IL-1ß concentration postchallenge, downregulated the mRNA expression of TNF-α, IL-1ß, IL-6, and TLR4 in the ileum and TLR4 and CFTR in the jejunum. Phosphorylation levels of NF-κB p65 and MAPK p38 were reduced in the ileum of piglets fed FA + ML diet. Supplementation of FA + ML increased the relative abundance of genera Lactobacillus especially Lactobacillus amylovorus species and decreased the genus abundances of Actinobacillus, unidentified Enterobacteriaceae, Moraxella. Collectively, the combination of formic acid and monolaurin in diets have the potential to be an antibiotic alternative to mitigate inflammatory response in piglets challenged with ETEC.

Increasing selenium supplementation to a moderately-reduced energy and protein diet improves antioxidant status and meat quality without affecting growth performance in finishing pigs.

BACKGROUND: Along with economic development and living standards' improvement, more and more attention has been converted from satisfying meat quantity to pursuing meat quality. RESEARCH PURPOSE: This study was conducted to evaluate the effects of increasing selenium (Se) supplementation to a moderately-reduced energy and protein diet (MREP) on growth performance, antioxidant status, meat quality in finishing pigs. BASIC PROCEDURES: A total of 144 "Duroc × Landrace × Yorkshire" pigs with the average body weight of 75 ± 1 kg were randomly allotted to 3 dietary treatments with six replicates per treatment and eight pigs per replicate. The 3 experimental diets were as follows: (1) Normal energy and protein (NEP) +0.2 mg/kg Se diet (14.02 MJ/kg DE, 14% CP and 0.2 mg/kg Se as selenite sodium), (2) MREP +0.2 mg/kg Se diet (13.60 MJ/kg DE, 13% CP and 0.2 mg/kg Se as selenite sodium), and (3) MREP +0.5 mg/kg Se diet (13.60 MJ/kg DE, 13% CP, 0.2 mg/kg Se as selenite sodium, and 0.3 mg/kg Se as Se-enriched yeast). The study lasted for 45 days. MAIN FINDINGS: The results show that there were no differences for growth performance, antioxidant status and meat quality of finishing pigs between NEP +0.2 mg/kg Se group and MREP +0.2 mg/kg Se group (P＞0.05). However, compared to pigs from MREP +0.2 mg/kg Se group, pigs from MREP +0.5 mg/kg Se group had greater Se concentration, GSH-Px activity and GSH concentration, but lower MDA concentration in serum (P＜0.05). Also, pigs from MREP +0.5 mg/kg Se group had greater Se concentration, T-AOC, and SOD activity, but lower MDA concentration in loin compared with pigs from MREP +0.2 mg/kg Se group (P＜0.05). As for meat quality, pigs from MREP +0.5 mg/kg Se group had greater a* value (relative redness) at 45 min and 24 h in loin compared with pigs from MREP +0.2 mg/kg Se group (P＜0.05). Compared to pigs from MREP +0.2 mg/kg Se group, pigs from MREP +0.5 mg/kg Se group had lower MDA concentration of fresh pork during a simulated retail display at 0, 1, 2, 4, 6 and 7 day (P＜0.05). PRINCIPAL CONCLUSIONS: In conclusion, increasing selenium supplementation to a moderately-reduced energy and protein diet improved antioxidant status and meat quality without affecting growth performance in finishing pigs. (New Aspects) The present study provided a nutritional strategy for reducing feed costs and improving pork quality without influencing growth performance in finishing pigs.

Immune Response of Piglets Receiving Mixture of Formic and Propionic Acid Alone or with Either Capric Acid or Bacillus Licheniformis after Escherichia coli Challenge.

This study aims to evaluate whether diets containing mixture of formic and propionic acid alone or supplemented with either capric acid or Bacillus Licheniformis can alleviate immune inflammatory response of piglets challenged with enterotoxigenic Escherichia coli (ETEC). A total of 30 weaning pigs were assigned to 5 diets, without additive (CON), with antibiotics (ATB), with 1% organic acid (OA; 64% formic and 25% propionic acid), with OA plus 0.2% capric acid (OA + CRA), and with OA plus 0.02% probiotic (Bacillus Licheniformis; OA + PB). After oral challenge with ETEC on day 10, the feces and plasma of all pigs were collected at different time points. Four additive treatments all decreased rectal temperature (RT) at 9 h and fecal scores (FS) at 24 h after challenge (P < 0.05), while at 9 h after challenge, inclusion of OA induced a decrease of RT compared with OA + CRA and OA + PB (P < 0.05). In plasma, concentration of interleukin (IL)-1ß was reduced with the addition of ATB and OA at 24 h and 48 h after challenge and it is lower in OA group than OA + CRA group at 24 h after challenge (P < 0.05). Diets with ATB, OA, and OA + PB caused a decrease of the concentrations of IL-6 in plasma at 9 h after challenge (P < 0.05). The four additives treated piglets showed decreased concentrations of plasma tumor necrosis factor-α and interferon-γ at 9 h and 24 h after challenge, respectively (P < 0.05). In conclusion, OA supplementation alleviated the inflammatory response and reduced diarrhea incidence in piglets challenged with ETEC. However, no further improvements were observed when OA supplemented with CRA or probiotics.

Increasing selenium supply for heat-stressed or actively cooled sows improves piglet preweaning survival, colostrum and milk composition, as well as maternal selenium, antioxidant status and immunoglobulin transfer.

This study aimed to evaluate the effects of increasing selenium (Se) supply for heat-stressed or actively cooled sows on sow productivity, colostrum and milk composition, as well as the selenium and antioxidant status and immunoglobulin levels of sows and nursing piglets. The study was a 2 × 2 factorial design, where the first factor was farrowing environment [heat stress vs. actively cooling, temperature: 29.61 ± 0.19 ℃ (27.70-31.60 ℃) vs. 27.90 ± 0.15 ℃ (26.90-30.20 ℃); temperature-humidity index: 72.91 ± 0.26 (70.30-75.70) vs. 70.81 ± 0.22 (69.30-73.80)], and the second factor was dietary Se level during late gestation and lactation [(0.3 vs. 1.2 mg/kg Se as Se-yeast, the basal diet was corn-soybean meal diet formulated according to NRC (2012) except for Se level]. Forty multiparous sows (Landrace × Yorkshire) were randomly allotted to 1 of 4 treatments (10 sows and following 90 piglets per treatment, respectively). The results show that: (1) There were no interactions of farrowing environment with Se treatments with the exceptions of nutrient content of 7-d milk; (2) As for zootechnical measures, piglets of sows receiving increasing Se tended to have greater preweaning survival compared with those of sows receiving control diet without interactions of environment and Se treatments; (3) As to colostrum and milk composition, greater concentrations of protein, lactose, solids-not-fat in colostrum, and greater fat concentration in 7-d and 14-d milk were found for sows fed increasing Se; (4) Regarding Se and antioxidant status, increasing Se supply for sows increased Se content in colostrum and 21-d milk, as well as in plasma of 1-day-old and 21-day-old piglets. Meanwhile, increasing Se supply for sows improved antioxidant status in colostrum (MDA content) and 21-d milk (T-AOC and MDA content), as well as in plasma of 1-day-old and 21-day-old piglets (GSH-Px activity and MDA content); (5) With regard to immunoglobulins, sows fed increasing Se had higher IgM levels in colostrum, and higher IgA in 21-d milk. Also, piglets from sows fed increasing Se had higher plasma IgA at 1 d of age, and higher IgA and IgG levels at 21 d of age. Collectively, increasing selenium supply for heat-stressed or actively cooled sows improved piglet preweaning survival, colostrum and milk composition, as well as maternal selenium, antioxidant status and immunoglobulin transfer irrespective of the climatic conditions, which indicates that Se requirements for sows should be urgently reassessed.

Fat encapsulation enhances dietary nutrients utilization and growth performance of nursery pigs.

Encapsulation of fat may facilitate digestion and absorption of fat in nursery pigs. Two experiments were conducted to evaluate 1) effects of encapsulation of palm oil (PO) and coconut oil (CO) on growth performance, feed intake, feed efficiency, and blood parameters, and 2) effects of encapsulation of PO and CO on apparent total tract digestibility (ATTD) of nutrients, and the activity of digestive enzymes in nursery pigs. In Exp. 1, 540 pigs (28 d of age, 8.23 ± 0.22 kg BW) were allotted to five treatments based on a randomized complete block design (as-fed basis). Pigs were fed basal diets with five different fat sources: 6.0% soybean oil (SBO), 6.0% PO, 6.0% PO from encapsulated fat (EPO), 6.0% CO, and 6.0% CO from encapsulated fat (ECO), respectively, with six pens per treatment and 18 pigs per pen for a 4-wk feeding trial. Dried casein and whey powder used for encapsulation were included at identical levels in all diets. Pigs fed EPO had increased (P < 0.05) ADG during days 0 to 14 and overall compared to pigs fed SBO and PO, whereas ADG of pigs fed ECO was not different from pigs fed EPO and CO. There were no differences in ADFI among treatments. Pigs fed EPO had increased G:F (P < 0.05) during days 0 to 14 compared to SBO, PO, and CO. Serum urea nitrogen concentrations in pigs fed EPO, CO, and ECO were lower (P < 0.05) than that of pigs fed SBO and PO. In Exp. 2, 30 pigs (28 d of age, 8.13 ± 0.10 kg BW) were housed individually (n = 6 per treatment) and allotted to five treatments as described in Exp.1. Pigs were fed ad libitum for 4 wk to measure ATTD of diets weekly and digestive enzyme activity at week 4. Pigs fed EPO, CO, and ECO had increased (P < 0.05) ATTD of DM and GE compared to pigs fed SBO and PO. Pigs fed SBO had reduced (P < 0.05) ATTD of CP compared to other treatments. Pigs fed PO had reduced (P < 0.05) ATTD of ether extracts (EE) compared to other treatments. Pigs fed PO had greater (P < 0.05) trypsin activity in the pancreas than pigs fed SBO and CO. Pigs fed PO tended to have lower (P = 0.073) pancreatic lipase activity compared to other treatments, whereas dietary treatments had no effect on pancreatic amylase activity. In conclusion, this study indicates that encapsulation of PO improved growth performance and ATTD of diets in nursery pigs, whereas the limited effects of encapsulated CO were likely due to the high digestibility of the medium-chain triglycerides abundant in CO.

Effect of pad-fan cooling and dietary organic acid supplementation during late gestation and lactation on reproductive performance and antioxidant status of multiparous sows in hot weather.

A 2 × 2 factorial arrangement (rearing room with or without pad-fan cooling × diet with or without 2.5 kg/t organic acid) was used to evaluate the effect of pad-fan cooling and dietary organic acid supplementation during perinatal period on reproductive performance and antioxidant status of sows in hot weather. This study was conducted in a subtropical city in Guangdong Province in South China between August and October, 2015. At day 85 of gestation, a total of 112 sows were randomly assigned to the four treatments with 28 sows per treatment, and maintained until day 21 of lactation, and the feeding trial lasted for 51 days. During the experimental period, room temperature and humidity were recorded hourly. The lactation feed intake of sows (P = 0.109) and stillbirths (P < 0.05) increased when the sows were reared in the room with the pad-fan cooling against the room without pad-fan cooling. The number of weak newborns per litter and the malondialdehyde content in days 14 and 21 milk decreased (P < 0.05), while the lactation feed intake of sows, weaned litter weights, and individual pig weights increased when the sows were fed the organic acid (P < 0.05). In conclusion, pad-fan cooling in rearing room improved the lactation feed intake of sows, and dietary organic acid supplementation improved reproductive performance and milk antioxidant status of sows. Pad-fan cooling is recommended in farrowing room, but not in gestating room.