The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective:To investigate the effect of self-made medical ventilation chair in patients with acute respiratory distress syndrome (ARDS) ventilated in prone position, with the aim of reducing the occurrence of complications in patients with ARDS ventilated in prone position.Methods:This study was a quasi experimental research method. In this study, 78 patients admitted to the respiratory intensive care unit of Changsha Central Hospital affiliated to South China University from October 2019 to September 2021 were selected for the study by convenience sampling method, and were divided into a control group and a experimental group according to the order of admission, with 39 cases in each group. The experimental group was ventilated in the prone position using a self-made medical ventilation chair, and the control group was ventilated in the prone position using the conventional turning method, comparing the facial skin injury, tracheal displacement, tracheal tube obstruction, and RICU hospitalization time in the two groups.Results:At the end of prone position ventilation, the incidence of facial skin intact and redness and swelling was 56.41% (22/39) and 43.59% (17/39) in the experimental group and 25.64% (10/39) and 69.23% (27/39) in the control group, respectively, with statistically significant differences ( χ2=7.63, 5.21, both P<0.05); there was no statistically significant difference in the incidence of facial skin breakdown between the two groups ( P>0.05); the incidence of complications was 5.13% (2/39) in the experimental group and 20.51% (8/39) in the control group, with statistically significant differences ( χ2=4.13, P<0.05); the duration of RICU stay was (13.34 ± 3.85) days in the experimental group and ( 15.80 ± 5.55) days, with a statistically significant difference ( t=2.25, P<0.05). Conclusions:The use of self-made medical ventilation chair can reduce the facial skin damage of patients, reduce the occurrence of related complications, and shorten the hospitalization time of RICU. It is worth popularizing and applying in ICU.

Objective:To study the feasibility, safety and technique for laparoscopic anatomical liver resection of segment 8.Methods:The clinical data of 9 patients who underwent laparoscopic anatomical liver resection of segment 8 from January 2015 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. There were 6 males and 3 females, with age ranging from 29 to 67 years (average 53.6 years). The operation time, intraoperative blood loss , postoperative hospital stay, postoperative complications, and long-term survival and recurrence rates on follow-up were analysed.Results:Laparoscopic anatomical liver resection of segment 8 was successfully carried out in these patients. The mean operative time was 188.9 min(range 140-240 min). The mean estimated intraoperative blood loss was 117.8 ml (range 20-300 ml). The postoperative hospital stay was 6.9 days (range 3-12 days). One patient developed pleural effusion after operation and responded to conservative treatment. Another patients developed ascites with delayed extubation. The patient was successfully treated with conservative treatment. No patients developed complications above Clavien Dindo Ⅲa. There were no perioperative deaths. The postoperative pathological results showed hepatocellular adenoma ( n=2), hepatocellular carcinoma ( n=4), cholangiocarcinoma ( n=1), and metastatic liver cancer ( n=2). On follow-up for 12-58 months (median 22 months) one patient with hepatocellular carcinoma developed recurrence at 18 months after operation and was treated with microwave ablation. The other patients were well on follow-up. Conclusions:With adequate preoperative evaluation, reasonable case selection, rigorous surgical planning, and skilled laparoscopic techniques, laparoscopic anatomical liver resection of segment 8 was safe and feasible, and the short-term efficacy was good in this study.

Objective:To evaluate fibrotic border guided anatomical hepatectomy in the treatment of hepatolithiasis complicated with atrophy-hypertrophy complex.Methods:One hundred and sixty-seven cases undergoing hepatectomy guided by the boundary of liver fibrosis in the treatment of hepatolithiasis complicated with atrophy-hypertrophy complex from Jan 2011 to Dec 2019 in Hunan Province Peopole's Hospital were reviewed.Results:All patients were successfully treated by anatomical hepatectomy under the guidance of the liver fibrosis boundary with intraoperative choledochoscopy,the operation time was (231.5±37.1) min and the average blood loss was (375.7±52.6) ml,the average hospital stay was (10.2±1.1) days,the residual stone rate was 8.9%, according to the scoring system of Clavien-Dindo, Grade Ⅰ complications occured in 86 cases, Grade Ⅱ complications occured in 35.Follow-up ranged from 3 to 107 months, 15 cases had recurrent stones,four were reoperated.Conclusions:Fibrotic border guided anatomical hepatectomy in the treatment of hepatolithiasis complicated with atrophy-hypertrophy complex is safe and effective.

Objective:To investigate the application value of P-loop digestive tract recons-truction in pancreaticoduodenectomy (PD).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 ampullary disease patients undergoing PD in the Liuzhou People′s Hospital Affiliated to Guangxi Medical University from April to December 2020 were collected. There were 13 males and 8 females, aged from 35 to 76 years, with a median age of 60 years. All the 21 patients underwent PD and digestive tract reconstruction using P-loop method based on the Child reconstruction. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect survival and discomfort symptoms of patients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or persentages. Results:(1) Surgical situations: all the 21 patients underwent PD successfully. The operation time, time of P-loop anastomosis and volume of intraoperative blood loss of 21 patients were (317±74)minutes, (14±3)minutes and 375 mL(range, 100-800 mL), respectively. Of the 21 patients, 17 cases had pancreatic texture as soft, 4 cases had pancreatic texture as hard, 3 cases had diameter of pancreas ≤3 mm, 18 cases had diameter of pancreas >3 mm, 14 cases were placed pancreatic duct stent, 7 cases were not placed pancreatic duct stent. (2) Postoperative situations: 2 of the 21 patients had grade A pancreatic fistula, and none of patient had grade B or grade C pancreatic fistula. One case had hepaticojejunal anastomotic fistula, 2 cases without pancreatic fistula had delayed gastric emptying and none of patient had abdominal infection or bleeding. The duration of postoperative hospital stay of 21 patients was (16±5)days, and none of patient died during postoperative 30 days. Results of postoperative histopathological examination showed there were 10 cases with duodenal papillary carcinoma, 4 cases with lower bile duct carcinoma, 3 cases with pancreatic head ductal adenocarcinoma, 1 case with duodenum stromal tumors, 1 case with gastric antrum carcinoma, 1 case with mass in the head of the pancreas of IgG4 and 1 case with choledochal cyst of type 3. (3) Follow-up: all 21 patients were followed up for 1.0 to 7.0 months, with a median follow-up time of 4.3 months. None of patient died. There was no abdominal pain, distension or dyspepsia during follow-up. One case was diagnosed as tumor liver metastasis at postoperative 5 months.Conclusion:P-loop digestive tract reconstruction in PD is safe and effective, with good short-term effect.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic diagnosis. METHODS: A male patient with achondroplasia due to a de novo FGFR3 variant was subjected to single sperm isolation and sequencing. Twenty single sperm samples were isolated by mechanical immobilization, and their whole genome was amplified. PCR primers were designed for the variant site and 25 flanking single nucleotide polymorphism (SNP) loci, and the PCR products were sequenced to determine the chromosomal haplotype which did not harbor the pathogenic variant. Biopsy samples of 12 embryonic trophoblasts were taken. Following whole genome amplification, high-throughput sequencing was carried out to detect the carrier status of the embryos. Wild type blastocysts were selected for transplantation. Amniotic fluid samples were taken at 19 weeks of gestation to confirm the status of the fetus. RESULTS: Eight SNP were selected by single sperm sequencing, with which the haplotypes were successfully constructed. Preimplantation genetic testing indicated that 5 embryos have carried the pathogenic variant and 7 did not. Testing of amniotic fluid sample during the second trimester of pregnancy confirmed that the fetus did not carry the FGFR3 gene c.1138G>A variant. CONCLUSION For male patients carrying de novo pathogenic variants, SNP sites can be selected through single sperm sequencing, and haplotypes can be constructed by linkage analysis for preimplantation genetic diagnosis.

Objective:To evaluate short-term therapeutic effect of surgical treatment for complicated hepatolithiasis under the guidance of 3D reconstruction.Methods:We retrospectively analyzed the clinical data of 56 patients with complicated hepatolithiasis undergoing surgical treatment with the guidance of 3D reconstruction at the Department of Hepatobiliary Surgery of Hunan Province People′s Hospital from Jan 2011 to Jun 2019.Results:All the patients were successfully operated on under the guidance of three-dimensional reconstruction and extraction of residual stones by choledochoscope. The average duration of operation was 210.3 minutes and the average blood loss was 350.6 ml. According to the scoring system of Clavien-Dindo, Grade Ⅰ complications occurred in 36 cases, Grade Ⅱ complications in 5 cases and there were no complications of Grade Ⅲ or higher. As found by an average follow-up of 3.6 years (range from 5 months to 8 years) , only one patient had reflux cholangitis .Although the rate of residual stone was 68.8%, most stones remained only in the end branch of bile duct, hence do not interfere much with the patients′ living status.Conclusions:The surgical treatment with the guidance of 3D reconstruction is of satisfactory short-term curative effect in complicated hepatolithiasis.

OBJECTIVE: To analyze the association of the clinical inflammatory indices with the severity of urinary sepsis. METHODS: We reviewed the clinical data of 70 patients with urinary sepsis treated in our hospital between January, 2013 and April, 2018. All the patients were diagnosed in line with the Guidelines for Diagnosis and Treatment of Urological Diseases in China (2014 edition), including 22 patients with sepsis, 12 with hypotension and severe sepsis, 17 with septic shock, and 19 with critical septic shock. White blood cell count (WBC), neutrophil percentage (N%), platelets (PLT), fibrinogen (FIB), Ddimer, interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were examined in all the cases and compared among the 4 groups. The correlations of these inflammatory markers with the severity of sepsis were analyzed using logistic regression analysis. RESULTS: The 4 groups of patients showed significant differences in N%, PLT, D-dimer, and PCT ( < 0.05) but not in CRP (>0.05). Kruskal-Wallis Pairwise comparisons showed that the N% and PCT in patients with sepsis differed significantly from those in the other 3 groups; platelets in patients with sepsis differed significantly from those in patients with septic shock and critical septic shock; D-dimer differed significantly between patients with sepsis and those with septic shock. Among the 4 groups, the median levels of PLT decreased and PCT and N% increased with the worsening of sepsis. Logistic regression analysis indicated that PCT (=0.186, =0.000), N% (=0.047, =0.035) and PLT (=-0.012, =0.003) were significantly correlated with the severity of sepsis in these patients. CONCLUSIONS PCT, PLT and N% are all significantly correlated with the severity of sepsis, and their combined detection can be informative for assessing the severity of sepsis to facilitate clinical decisions on treatment.
Biomarkers ; blood ; C-Reactive Protein ; analysis ; China ; Fibrin Fibrinogen Degradation Products ; analysis ; Fibrinogen ; analysis ; Humans ; Interleukin-6 ; blood ; Leukocyte Count ; Platelet Count ; Procalcitonin ; blood ; Sepsis ; blood ; diagnosis ; Severity of Illness Index ; Shock, Septic ; blood ; diagnosis ; Statistics, Nonparametric ; Urinary Tract Infections ; diagnosis

OBJECTIVE: To optimize the condition for chromosome flaking of mesenchymal stem cells to ensure the cytogenetic quality control of expanding production and clinical application. METHODS: Chromosomal flaking methods were optimized from current chromosome preparation techniques from the aspects of MSCs cell culture concentration, colchicine treatment time and low permeability time. RESULTS: By repeated pre-experiments, the optimal MSCS chromosome flaking condition of MSCs was determined as cell culture concentration of (1-2)× 10 cells per T25 cell culture bottle, and the colchicines processing time was determined as 2 hours and 10 minutes, and the low permeability was 1 hour. CONCLUSION The optimized chromosome flaking condition can fulfill the requirement of cytogenetic quality control for MSCs.
Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Chromosome Disorders ; Chromosomes, Human ; Cytogenetics ; Humans ; Mesenchymal Stem Cells

BACKGROUND: Inducing factors are currently used as a main method for the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes. OBJECTIVE: To investigate the collaborative stimulation of transforming growth factor beta1 (TGF-β1) and insulin-like growth factor 1 (IGF-1) to induce the directed differentiation of BMSCs to chondrocytes, and to explore the best inductive effect. METHODS: Rat BMSCs were isolated, cultured and purified using adherent culture. Then, different inducing factors were added in the induction medium: TGF-β1+IGF-1 group, TGF-β1 group, IGF-1 group, and control group without growth factors. Immunofluorescence was carried out at 21 days of induction. The expression of collagen type Ⅱ was evaluated by immuncytochemical staining at 7, 14 and 21 days of induction. RESULTS AND CONCLUSION: (1) Immunofluorescence detection of the TGF-β1+IGF-1 and TGF-β1 groups showed highly expressed collagen type Ⅱ (brown red-stained cytoplasm), while negatively expressed collagen type Ⅱ in the other two groups. (2) Findings from the immuncytochemical staining showed that the expression of collagen type Ⅱ was stronger in the TGF-β1+IGF-1 group than the TGF-β1 group (P < 0.01), and the expression was gradually enhanced with time. Meanwhile, there was also no expression of collagen type Ⅱ in the IGF-1 and control groups. To conclude, the combination of TGF-β1 and IGF-1 can achieve the better inductive effect on the chondrogenic differentiation of BMSCs in vitro.