Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

To report a case of Noonan-like syndrome with loose anagen hair, and to detect gene mutations in the family. A 3-year-old female patient presented with a special facial appearance, short stature, deep palmar and plantar creases, and dark skin. The scalp hair was sparse and thin, dermoscopy showed black spot sign, single-hair follicular units, hair shafts varying in the diameter, upright hair and new vellus hair, and constriction of hair shafts and nodular hair were occasionally observed. Peripheral blood samples were collected from the proband and her parents, and the genomic DNA was extracted for whole-exome sequencing. A heterozygous missense mutation c.4A>G was identified in exon 2 of the SHOC2 gene in the proband, resulting in the substitution of serine by glycine at amino acid position 2 (p.S2G) . The mutation was not identified in either of her parents. Combined with the clinical phenotype and gene mutation, the diagnosis of Noonan-like syndrome with loose anagen hair was confirmed.

Chronic heart failure is the terminal stage of progressive aggravation of various cardio-vascular diseases,and as an independent risk factor for heart failure,senility can increase the preva-lence rate.Ventricular remodeling is the main pathological and physiological basis of chronic heart failure,and in addition to changes in the activities of inflammatory reactions and related cytokines,factors such as metabolic disorders of myocardium,regulation of myocardial extracellular vesicles,and imbalance of intestinal microbiota also play important roles.This paper provided an overview of the research progress on ventricular remodeling mechanism in elderly patients with heart failure.

Chronic heart failure is the terminal stage of progressive aggravation of various cardio-vascular diseases,and as an independent risk factor for heart failure,senility can increase the preva-lence rate.Ventricular remodeling is the main pathological and physiological basis of chronic heart failure,and in addition to changes in the activities of inflammatory reactions and related cytokines,factors such as metabolic disorders of myocardium,regulation of myocardial extracellular vesicles,and imbalance of intestinal microbiota also play important roles.This paper provided an overview of the research progress on ventricular remodeling mechanism in elderly patients with heart failure.

With the arrival of the era of big data, increasing attention has been drawn to the application of artificial intelligence (AI) in the medical field. AI has many advantages, such as objectivity, accuracy, minimal invasiveness, time savings and high efficiency. Therefore, the combination of AI with dental diagnosis and treatment can help dentists improve work efficiency and save medical resources, offering potential significant benefits for dental application. At present, AI has been gradually integrated into prosthodontics, oral and maxillofacial surgery, orthodontics, endodontics and periodontics. The AI system can realize automatic tooth preparation, automatic tooth arrangement and implantology. Deep learning can be used to assist in diagnosing maxillary sinus inflammation, predicting the complications of tooth extraction and improving the accuracy of osteotomy. The AI system can also provide significant clues for the diagnosis, treatment and prognosis of oral and maxillofacial tumors. The breakthrough brought by AI in cephalometric and the assessment of facial attractiveness of patients has promoted the development of intelligent and personalized orthodontic treatment. Deep learning and analysis of medical images also promote the accuracy of root canal therapy as well as the diagnosis and treatment of periodontal diseases. AI technology has realized the leap from digitalization to automation and intelligence in oral diagnosis and treatment, and its application potential in the oral field should not be underestimated. Based on the concepts of AI, this paper will focus on the application of artificial intelligence in various oral clinical fields and briefly introduce its advantages, problems and future.

Liposomes are spherical vesicles with bilayer membrane structure spontaneously formed by phospholipids dispersed in an aqueous medium. Liposomes are excellent drug carrier with amphiphilic properties. Liposomes have good biocompatibility, biodegradability and no immunogenicity. Liposomes can achieve the delivery of the drug, enhance the solubility, improve the stability, reduce the toxic effect of the drug, and improve the therapeutic effect of the loaded drug. In recent years, liposome drug delivery systems have been widely used in dentistry. This article reviews the application of liposome drug delivery systems in caries, dental pulp diseases, periodontitis, implantation, oral anesthesia and oral candidiasis.

Objective:To select the animal model more consistent with the pathophysiology of abdominal compartment syndrome (ACS) through the comparative study of the methods of multiple water sacs superimposed compression and gas perfusion.Methods:Ten experimental pigs were randomly divided into two groups ( n = 5): the "constant volume model" (constant volume model group) and the "constant pressure model" (constant pressure model group) of intra-abdominal hypertension. The models were prepared by the method of water sac superposition and pressurization, and artificial pneumoperitoneum respectively. The abdominal pressures of both groups were 25 mmHg (1 mmHg = 0.133 kPa) and observed for 4 hours. The pressure was measured once an hour for 4 hours and the pressure-time curves of the two groups were drawn respectively. The experimental animals were sacrificed 4 hours after modeling. The heart and lung were harvested, and the histopathological changes were observed by hematoxylin-eosin (HE) staining. Results:Two groups of experimental pigs were successfully modeled. The abdominal pressure gradually increased at 0, 1, 2, 3, 4 hours after operation in the constant volume model group (mmHg: 25.0±0, 27.1±0.2, 29.4±0.1, 30.9±0.2, 33.1±0.1), and there was a positive correlation between the abdominal pressure and time (functional equation: Y1 = 25.102 0+1.996 0 X1; R2 = 0.996 2, P = 0.000 1). The abdominal pressure value in the constant pressure model group at 0, 1, 2, 3, 4 hours were maintained 25 mmHg, and there was no linear correlation between the abdominal pressure and time (functional equation: Y2 = 25). HE staining showed that in the constant volume model group, the myocardial fibers were accompanied with hyaline degeneration, significantly reduced transverse lines, part of myocardial fiber atrophy, and visible nuclear aggregation; hemorrhage, chronic inflammatory cell infiltration and inflammatory exudation were found in the lung tissues. In the constant pressure model group, partial atrophy of myocardial fiber, partial hypertrophy, focal hyaline degeneration, disappearance of local striae, hyaline degeneration of myocardial fiber, dilation and congestion of intermyocardial artery were observed. Slight hyperplasia of alveolar epithelium in some areas, heart failure cells, dilation and congestion of bronchi and trachea artery, a large number of red blood cells and uniform light staining substances in lumen were found. Conclusion:After the model was made by the method of multiple water sacs, the pressure of the abdominal cavity continued to increase with the development of the disease, which was in line with the clinical pathological changes of ACS, and was more suitable for making the animal model of the intra-abdominal hypertension.

Objective:To analyze the incidence of postoperative pulmonary complications and related factors in elderly patients after major abdominal surgery.Methods:Clinical data of elderly patients undergone major abdominal surgeries at Beijing Hospital were retrospectively analyzed.The incidence of postoperative pulmonary complications was studied, and related factors were analyzed using Logistic regression analysis.Results:A total of 96 cases were included.The incidence of postoperative pulmonary complications was 53.1%(51/96)in elderly patients after major abdominal surgery.Logistic regression analysis showed laparoscopy was a protective factor for postoperative pulmonary complications( OR=0.293, 95% CI: 0.100-0.865, P=0.026), while driving pressure > 18 cmH 2O(1 cmH 2O=0.098 kPa)( OR=3.300, 95% CI: 1.148-9.434, P=0.027)and intraoperative bleeding volume > 500 ml( OR=4.444, 95% CI: 1.091-18.180, P=0.037)were risk factors for postoperative pulmonary complications. Conclusions:Attention should be paid to the incidence of postoperative pulmonary complications in elderly patients after major abdominal surgery.Laparoscopy is a protective factor for postoperative pulmonary complications, while driving pressure more than 18 cmH 2O and intraoperative bleeding volume more than 500 ml can increase the risk of postoperative pulmonary complications.

Objective: To assess the association of single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) with refractory epilepsy in children. Methods: Peripheral blood samples were collected from 200 children with epilepsy and 100 healthy controls. Genomic DNA was extracted and subjected to PCR amplification, agarose gel electrophoresis and target site sequencing. Genotypes of rs1922242, rs2235048, rs10808072, rs868755 and rs1202184 loci of the MDR1 gene were analyzed. Results: No significant difference was found in genotypic distribution and allelic frequencies of the rs1922242, rs2235048, rs10808072 and rs868755 loci between the drug-resistant and drug-sensitive groups. For the rs1202184 locus, a significant difference in genotypic distribution was found (P = 0.008). No significant difference was found in the frequencies of various haplotypes between the two groups. Conclusion Genotypes of the rs1202184 locus of the MDR1 gene are associated with refractory epilepsy in children, for which the AA genotype plays a dominant role.