Objective To explore the development of new formulations new pharmaceutical cocrystal by combining hot melt extrusion and 3D printing technologies.Methods The insoluble drug ibuprofen and nicotinamide were selected as model drugs,and hot melt extrusion was applied to extrude ibuprofen-nicotinamide cocrystal by regulating the processing temperature,screw speed and residence time,etc.Hot-stage polarized light microscopy,powder X-ray diffraction,differential scanning calorimetry,Fourier transform infrared spectroscopy,and Raman spectroscopy were used for characterization analysis.The process research was carried out by investigating properties such as eutectic particle size and distribution,angle of repose,and vibrational solidity density.On this basis,two 3D printing techniques,fused deposition molding and selective laser sintering type,were selected for pharmaceutical cocrystal loaded sheet printing.Results A new formulation of pharmaceutical cocrystal tablets loaded with ibuprofen-nicotinamide was successfully printed through the combined application of hot-melt extrusion and 3D printing technologies.Conclusions Combined process of hot melt extrusion and 3D printing technology in the field of developing new pharmaceutical cocrystal formulations,laying the material foundation and scientific support for the development of new pharmaceutical cocrystal formulations with personalized and programmable release on demand.

Objective To investigate the effect of early closed reduction and percutaneous Kirschner wire pinning for Gartland type Ⅱ and Ⅲ pediatric supracondylar humerus fractures.Methods Clinical data of 123 children with Gartland type Ⅱ and Ⅲsupracondylar humerus fractures admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed.According to the time from injury to operation,they were divided into early group(≤ 24 h)and delayed group(＞24 h).The perioperative conditions,postoperative complications,fracture healing,and elbow joint functional recovery were compared between the two groups.Results Compared to the delayed group,the early group had less operation time[(22.9±11.3)min vs.(40.3±17.5)min,t=-6.116,P=0.000],less number of intraoperative fluoroscopy[(10.6±4.5)times vs.(17.4±5.5)times,t=-7.471,P=0.000],shorter hospital stay[(3.3±1.0)d vs.(4.2±1.3)d,t=-3.866,P=0.000],and less hospitalization cost[(10 555.0±971.2)yuan vs.(10 972.4±938.9)yuan,t=-2.345,P=0.021].The rate of anatomical reduction in the early group was higher than that in the delayed group[79.0％(60/76)vs.59.6％(28/47),x2=5.354,P=0.021].No serious complications such as vascular and nerve injury,compartment syndrome,ischemic myosclerosis,myositis ossificans,or cubitus varus and valgus occurred in both group after surgery.The incidences of tension blisters[6.6％(5/76)vs.23.4％(11/47),x2=7.265,P=0.007],plaster loosening[22.4％(17/76)vs.40.4％(19/47),x2=4.574,P=0.032],and pin tract infection[2.6％(2/76)vs.14.9％(7/47),x2=4.757,P=0.029]in the early group were lower than those in the delayed group.The fracture union time,and the time to start active and full weight-bearing activities in the early group were earlier than those in the delayed group(P＜0.05).The Flynn elbow joint scores at 3 and 6 months after surgery in the early group were better than those in the delayed group(Z=-3.469,P=0.001;Z=-2.961,P=0.003).Conclusion Early closed reduction and percutaneous Kirschner wire pinning is effective in the treatment of pediatric supracondylar humerus fractures,which can shorten the operation time and hospital stay,reduce the hospitalization cost,lower the incidence of complications,and restore elbow joint function in early stage.

Objective To investigate the effect of early closed reduction and percutaneous Kirschner wire pinning for Gartland type Ⅱ and Ⅲ pediatric supracondylar humerus fractures.Methods Clinical data of 123 children with Gartland type Ⅱ and Ⅲsupracondylar humerus fractures admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed.According to the time from injury to operation,they were divided into early group(≤ 24 h)and delayed group(＞24 h).The perioperative conditions,postoperative complications,fracture healing,and elbow joint functional recovery were compared between the two groups.Results Compared to the delayed group,the early group had less operation time[(22.9±11.3)min vs.(40.3±17.5)min,t=-6.116,P=0.000],less number of intraoperative fluoroscopy[(10.6±4.5)times vs.(17.4±5.5)times,t=-7.471,P=0.000],shorter hospital stay[(3.3±1.0)d vs.(4.2±1.3)d,t=-3.866,P=0.000],and less hospitalization cost[(10 555.0±971.2)yuan vs.(10 972.4±938.9)yuan,t=-2.345,P=0.021].The rate of anatomical reduction in the early group was higher than that in the delayed group[79.0％(60/76)vs.59.6％(28/47),x2=5.354,P=0.021].No serious complications such as vascular and nerve injury,compartment syndrome,ischemic myosclerosis,myositis ossificans,or cubitus varus and valgus occurred in both group after surgery.The incidences of tension blisters[6.6％(5/76)vs.23.4％(11/47),x2=7.265,P=0.007],plaster loosening[22.4％(17/76)vs.40.4％(19/47),x2=4.574,P=0.032],and pin tract infection[2.6％(2/76)vs.14.9％(7/47),x2=4.757,P=0.029]in the early group were lower than those in the delayed group.The fracture union time,and the time to start active and full weight-bearing activities in the early group were earlier than those in the delayed group(P＜0.05).The Flynn elbow joint scores at 3 and 6 months after surgery in the early group were better than those in the delayed group(Z=-3.469,P=0.001;Z=-2.961,P=0.003).Conclusion Early closed reduction and percutaneous Kirschner wire pinning is effective in the treatment of pediatric supracondylar humerus fractures,which can shorten the operation time and hospital stay,reduce the hospitalization cost,lower the incidence of complications,and restore elbow joint function in early stage.

Objective To explore the development of new formulations new pharmaceutical cocrystal by combining hot melt extrusion and 3D printing technologies.Methods The insoluble drug ibuprofen and nicotinamide were selected as model drugs,and hot melt extrusion was applied to extrude ibuprofen-nicotinamide cocrystal by regulating the processing temperature,screw speed and residence time,etc.Hot-stage polarized light microscopy,powder X-ray diffraction,differential scanning calorimetry,Fourier transform infrared spectroscopy,and Raman spectroscopy were used for characterization analysis.The process research was carried out by investigating properties such as eutectic particle size and distribution,angle of repose,and vibrational solidity density.On this basis,two 3D printing techniques,fused deposition molding and selective laser sintering type,were selected for pharmaceutical cocrystal loaded sheet printing.Results A new formulation of pharmaceutical cocrystal tablets loaded with ibuprofen-nicotinamide was successfully printed through the combined application of hot-melt extrusion and 3D printing technologies.Conclusions Combined process of hot melt extrusion and 3D printing technology in the field of developing new pharmaceutical cocrystal formulations,laying the material foundation and scientific support for the development of new pharmaceutical cocrystal formulations with personalized and programmable release on demand.

AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P＜0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.

In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5％,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.

AIM:This study aims to investigate the expression differences of the ultraconserved RNA gene cluster uc.102-uc.106 and its host gene Obg-like ATPase 1(OLA1)in various tissues of C57BL/6J mice.METHODS:Five healthy male C57BL/6J mice aged 8～10 weeks were selected,and under normal physiological conditions,various tis-sues and organs,including liver,testis,bone marrow,brain,kidney,blood,lung,colon,thymus,spleen,stomach,heart,lymph nodes and bladder,were collected.Simultaneously,magnetic bead separation technology was employed to extract bone marrow blood cells,including B cells,macrophages,erythroid precursor,and mature red blood cells.The ex-pression levels of uc.102-uc.106 and OLA1 mRNA were determined by RT-qPCR with GAPDH as the internal reference.RESULTS:The OLA1 mRNA exhibited high expression levels in the brain,lymph nodes,testis and thymus of C57BL/6J mice,and low expression levels in the liver,spleen,lung,colon and peripheral blood(P<0.05).The expression trend of the uc.102-uc.106 gene cluster was generally opposite to that of OLA1 mRNA,except for both exhibiting high expression levels in testicular tissue(P<0.05).In blood cells,the OLA1 mRNA and the uc.102-uc.106 gene cluster showed the highest expression levels in B cells and the lowest expression levels in mature red blood cells(P<0.05).CONCLU-SION:This study indicates that OLA1 gene and uc.102-uc.106 gene cluster are expressed in different tissues and blood cells of C57BL/6J mice.Notably,the high expression levels of OLA1 gene and uc.102-uc.106 gene cluster in the mouse testis suggest a potential association with male reproductive functions.

【Objective】 To explore the feasibility, safety and clinical application value of laparoscopic radical rectal cancer surgery with natural orifice specimen extraction (NOSE) by comparing the postoperative pathological data, surgery-related variables and postoperative recovery between laparoscopic radical rectal cancer surgery with NOSE and laparoscopic-assisted radical rectal cancer surgery. 【Methods】 A retrospective analysis was conducted on 74 patients who underwent radical rectal cancer surgery with anus preservation in the Department of General Surgery of The First Affiliated Hospital of Xi’an Jiaotong University from July 2017 to April 2022. Among them, 38 cases underwent surgery with specimen extraction through an abdominal auxiliary incision (auxiliary incision group), and 36 cases underwent surgery with specimen extraction through a natural orifice (NOSES group). The differences in the efficacy of the two surgeries were evaluated by comparing the postoperative pathological data, surgical variables, and postoperative recovery of the two groups. 【Results】 There were no statistically significant differences in general data and postoperative pathological data between the two groups (all P>0.05). The NOSES group exhibited significantly shorter operative time, time to first flatus, time to first oral intake postoperatively, and postoperative hospital stay compared to the auxiliary incision group (all P<0.05). However, there were no statistically significant differences in intraoperative blood loss, postoperative complications, and whether secondary surgeries were performed (all P>0.05). 【Conclusion】 Laparoscopic surgery with NOSE for rectal cancer is safe and feasible with minimally invasive and accelerated recovery, which is worth promoting and applying in clinical practice.

This article reported a male patient with neonatal onset mental retardation autosomal dominant 35 (MRD35). The boy presented with repeated convulsions, hypotonia, enlarged head circumference, congenital muscular torticollis and feeding difficulties in the neonatal period. Dynamic electroencephalogram showed paroxysmal epileptic discharges in the left central-temporal region. High-throughput whole-exome sequencing revealed a heterozygous mutation of c.139G>A (p.Glu47Lys) in the PPP2R5D gene, which was a de novo mutation not inherited from his parents. The child had significant developmental delay at the age of one year. MRD35 lacks typical clinical manifestations and requires whole-exome sequencing for definitive diagnosis. Currently, there is no specific treatment for MRD35 and symptomatic treatments, including rehabilitation training, language training and seizure control, are mostly adopted.

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.