ObjectiveTo investigate the molecular mechanism of action of artemisinin in attenuating asthmatic airway inflammation and airway remodeling through the phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. MethodFifty male SD rats were randomly divided into blank group， model group， and low-dose， medium-dose， and high-dose groups of artemisinin， with 10 rats in each group. The ovalbumin （OVA）-induced asthma model of the rats was established， and after successful modeling， the blank group and model group received tail vein injection of 1.0 mL·kg^-1 normal saline， while the low-dose， medium-dose， and high-dose groups of artemisinin received tail vein injection of 12.5， 25， and 50 mg·kg^-1 artemisinin daily for seven days. Airway resistance was measured by the acetylcholine chloride method. Cell number and species changes in the alveolar lavage fluid of each group were determined by flow cytometry. Morphological changes in airway endothelial tissue were determined by the hematoxylin-eosin （HE） staining method. Apoptosis was determined by CytoTox 96 method， and enzyme-linked immunosorbent assay （ELISA） method was used to determine the NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， interleukin-1β （IL-1β）， and interleukin-10 （IL-10） expression. Western blot method was used to detect the （p）-PI3K/p-Akt level in the alveolar bronchial tissue of each group. ResultCompared with the blank group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly higher in the model group （P<0.05）. HE staining showed that the airway mucosa of the rats had obvious edema， and a large number of inflammatory cells were infiltrated （P<0.05）. The rate of apoptosis was significantly higher （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 increased significantly （P<0.05）. p-PI3K/p-Akt level increased significantly （P<0.05）. Compared with the model group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly decreased after the intervention of artemisinin at low， medium， and high concentrations （P<0.05）. HE staining showed that the degree of edema of the airway mucosa of the rats was reduced， and the area of the inflammatory cell infiltration was drastically reduced （P<0.05）. The apoptosis rate was significantly reduced （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 decreased significantly （P<0.05）. p-PI3K/p-Akt level decreased significantly （P<0.05）. ConclusionArtemisinin significantly inhibits NLRP3 inflammasome activation， reduces cellular pyroptosis and inflammatory cell expression， and attenuates airway inflammatory manifestations and airway remodeling in asthmatic rats， which may be related to the regulation of p-PI3K/p-Akt， and the results may provide laboratory insights and basis for the treatment of bronchial asthma with artemisinin.

Objective:To investigate the influences of age-adjusted Charlson comorbidity index (ACCI) on prognosis of patients undergoing laparoscopic radical gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 242 gastric cancer patients who underwent laparoscopic radical gastrectomy in 19 hospitals of the Chinese Laparoscopic Gastrointestinal Surgery Study Group-04 study, including 54 patients in Fujian Medical University Union Hospital, 32 patients in the First Hospital of Putian City, 32 patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 31 patients in Zhangzhou Affiliated Hospital of Fujian Medical University, 17 patients in Nanfang Hospital of Southern Medical University, 11 patients in the First Affiliated Hospital with Nanjing Medical University, 8 patients in Qinghai University Affiliated Hospital, 8 patients in Meizhou People′s Hospital, 7 patients in Fujian Provincial Hospital, 6 patients in Zhongshan Hospital of Fudan University, 6 patients in Longyan First Hospital, 5 patients in the First Affiliated Hospital of Xinjiang Medical University, 5 patients in the First Hospital Affiliated to Army Medical University, 4 patients in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 4 patients in West China Hospital of Sichuan University, 4 patients in Beijing University Cancer Hospital, 3 patients in the First Affiliated Hospital of Xiamen University, 3 patients in Guangdong Provincial People′s Hospital, 2 patients in the First Affiliated Hospital of Xi′an Jiaotong University, from September 2016 to October 2017 were collected. There were 193 males and 49 females, aged 62(range, 23?74)years. Observation indicators: (1) age distribution, comorbidities and ACCI status of patients; (2) the grouping of ACCI and comparison of clinicopathological characteristics of patients in each group; (3) incidence of postoperative early complications and analysis of factors affecting postoperative early complications; (4) follow-up; (5) analysis of factors affecting the 3-year recurrence-free survival rate of patients. Follow-up was conducted using outpatient examination or telephone interview to detect postoperative survival of patients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametric rank sum test. The X-Tile software (version 3.6.1) was used to analyze the best ACCI grouping threshold. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-Rank test was used for survival analysis. The Logistic regression model was used to analyze the factors affecting postoperative early complications. The COX proportional hazard model was used for univariate and multivariate analyses of factors affecting the 3-year recurrence-free survival rate of patients. Multivariate analysis used stepwise regression to include variables with P<0.05 in univariate analysis and variables clinically closely related to prognosis. Results:(1) Age distribution, comor-bidities and ACCI status of patients. Of the 242 patients, there were 28 cases with age <50 years, 68 cases with age of 50 to 59 years, 113 cases with age of 60 to 69 years, 33 cases with age of 70 to 79 years. There was 1 patient combined with mild liver disease, 1 patient combined with diabetes of end-organ damage, 2 patients combined with peripheral vascular diseases, 2 patients combined with peptic ulcer, 6 patients combined with congestive heart failure, 8 patients combined with chronic pulmonary diseases, 9 patients with diabetes without end-organ damage. The ACCI of 242 patients was 2 (range, 0-4). (2) The grouping of ACCI and comparison of clinicopathological characteristics of patients in each group. Results of X-Tile software analysis showed that ACCI=3 was the best grouping threshold. Of the 242 patients, 194 cases with ACCI <3 were set as the low ACCI group and 48 cases with ACCI ≥3 were set as the high ACCI group, respectively. Age, body mass index, cases with preoperative comorbidities, cases of American Society of Anesthesiologists classification as stage Ⅰ, stage Ⅱ, stage Ⅲ, tumor diameter, cases with tumor histological type as signet ring cell or poorly differentiated adenocarcinoma and cases with tumor type as moderately or well differentiated adenocarcinoma, cases with tumor pathological T staging as stage T1, stage T2, stage T3, stage T4, chemotherapy cycles were (58±9)years, (22.6±2.9)kg/m 2, 31, 106, 85, 3, (4.0±1.9)cm, 104, 90, 16, 29, 72, 77, 6(4,6) in the low ACCI group, versus (70±4) years, (21.7±2.7)kg/m 2, 23, 14, 33, 1, (5.4±3.1)cm, 36, 12, 3, 4, 13, 28, 4(2,5) in the high ACCI group, showing significant differences in the above indicators between the two groups ( t=-14.37, 1.98, χ2=22.64, Z=-3.11, t=-2.91, χ2=7.22, Z=-2.21, -3.61, P<0.05). (3) Incidence of postoperative early complications and analysis of factors affecting postoperative early complications. Of the 242 patients, 33 cases had postoperative early complications, including 20 cases with local complications and 16 cases with systemic complica-tions. Some patients had multiple complications at the same time. Of the 20 patients with local complications, 12 cases had abdominal infection, 7 cases had anastomotic leakage, 2 cases had incision infection, 2 cases had abdominal hemorrhage, 2 cases had anastomotic hemorrhage and 1 case had lymphatic leakage. Of the 16 patients with systemic complications, 11 cases had pulmonary infection, 2 cases had arrhythmias, 2 cases had sepsis, 1 case had liver failure, 1 case had renal failure, 1 case had pulmonary embolism, 1 case had deep vein thrombosis, 1 case had urinary infection and 1 case had urine retention. Of the 33 cases with postoperative early complications, there were 3 cases with grade Ⅰ complications, 22 cases with grade Ⅱ complications, 5 cases with grade Ⅲa complications, 2 cases with grade Ⅲb complications and 1 case with grade Ⅳ complica-tions of Clavien-Dindo classification. Cases with postoperative early complications, cases with local complications, cases with systemic complications were 22, 13, 9 in the low ACCI group, versus 11, 7, 7 in the high ACCI group, respectively. There were significant differences in cases with postoperative early complications and cases with systemic complications between the two groups ( χ2=4.38, 4.66, P<0.05), and there was no significant difference in cases with local complications between the two groups ( χ2=2.20, P>0.05). Results of Logistic regression analysis showed that ACCI was a related factor for postoperative early complications of gastric cancer patients undergoing laparoscopic radical gastrectomy [ odds ratio=2.32, 95% confidence interval ( CI) as 1.04-5.21, P<0.05]. (4) Follow-up. All the 242 patients were followed up for 36(range,1?46)months. During the follow-up, 53 patients died and 13 patients survived with tumor. The 3-year recurrence-free survival rate of the 242 patients was 73.5%. The follow-up time, cases died and cases survived with tumor during follow-up, the 3-year recurrence-free survival rate were 36(range, 2-46)months, 29, 10, 80.0% for the low ACCI group, versus 35(range, 1-42)months, 24, 3, 47.4% for the high ACCI group. There was a significant difference in the 3-year recurrence-free survival rate between the two groups ( χ2=30.49, P<0.05). (5) Analysis of factors affecting the 3-year recurrence-free survival rate of patients. Results of univariate analysis showed that preoperative comorbidities, ACCI, tumor diameter, histological type, vascular invasion, lymphatic invasion, neural invasion, tumor pathological TNM staging, postoperative early complications were related factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy [ hazard ratio ( HR)=2.52, 3.64, 2.62, 0.47, 2.87, 1.90, 1.86, 21.77, 1.97, 95% CI as 1.52-4.17, 2.22-5.95, 1.54-4.46, 0.27-0.80, 1.76-4.70, 1.15-3.12, 1.10-3.14, 3.01-157.52, 1.11-3.50, P<0.05]. Results of multivariate analysis showed that ACCI, tumor pathological TNM staging, adjuvant chemotherapy were indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy ( HR=3.65, 11.00, 40.66, 0.39, 95% CI as 2.21-6.02, 1.40-86.73, 5.41-305.69, 0.22-0.68, P<0.05). Conclusions:ACCI is a related factor for post-operative early complications of gastric cancer patients undergoing laparos-copic radical gastrectomy. ACCI, tumor pathological TNM staging, adjuvant chemotherapy are indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy.

Ubiquitination is a post-translational modification of proteins in eukaryotes, which mediates the specific degradation and signal transduction of proteins to regulate a variety of life processes and thus affects functions of the body. The disorder and imbalance of ubiquitination network is a major cause of serious human diseases. Ubiquitin molecules can form eight homogeneous ubiquitin chains with different topological structures, which vary greatly in abundance and function. At present, the classical ubiquitin chains K48 and K63 with high abundance and rich substrates have been intensively studied, while other atypical ubiquitin chains with low content remain to be studied. However, it has been proved that atypical ubiquitin chains play a key role in intracellular regulation. K6 is an important atypical ubiquitin chain, which is similar to K48 chain and has a tight spatial structure. It plays a role in DNA damage repair, mitochondrial quality control, the occurrence and development of tumor, and the pathogenesis of Parkinson's disease. Due to the lack of specific antibodies and effective enrichment methods for K6, little is known about its substrate and regulatory mechanism. This paper systematically reviews the structural characteristics, regulatory mechanism, biological functions, and relevant diseases of atypical K6 linkages, aiming to provide reference for the functional study of K6.
Humans ; Protein Processing, Post-Translational ; Signal Transduction ; Ubiquitin/chemistry* ; Ubiquitination

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

Objective: To compare the short-term clinical outcomes and cost differences of robotic distal pancreatectomy (RDP) versus laparoscopic distal pancreatectomy (LDP). Methods: The retrospective descriptive study was adopted.The clinical data of 158 patients underwent minimally invasive distal pancreatectomy who were admitted to Fujian Medical University Union Hospital between January 2016 and July 2018 were collected.A 1∶1 matched propensity score (PSM) analysis was performed for the RDP group and the LDP group.Observed indexes included operative time, blood loss, spleen-preserving rate, postoperative hospital stay, morbidity, incidence of pancreatic fistula and hospital costs. T test or rank sum test was used to compare measurement data, χ² test or Fisher exact test was used to compare count data. Results: A well-balanced cohort of 41 patients was analyzed.There were 14 males and 27 females in the RDP group, aged (45.2±16.4)years. There were 15 males and 26 females in the LDP group, aged (47.4±14.9) years.The operation time was (209.7±52.9) minutes for the RDP group and (186.5±56.7) minutes for the LDP group (P=0.073). Median blood loss was less in RDP (50(15-175)ml) compared with LDP (100(50-350)ml) (Z=-2.689, P=0.007). Thirty-eight cases of non-malignant diseases were observed in each group and spleen-preserving rate was higher in RDP (76.3%) compared to LDP(44.7%) (χ²=7.930, P=0.005).Postoperative hospital stay was similar in the RDP group and the LDP group (RDP: 9.4 days vs. LDP: 10.6 days; P=0.372). The overall morbidity and incidence of pancreatic fistula major complication rates (RDP: 12.2% vs. LDP: 14.6%, P=0.746; RDP: 7.3% vs. LDP: 9.8%, P=1.000) were similar.Total cost of RDP group was higher than that of LDP group ((80 563.7±10 641.8) yuan vs. (57 792.8±8 943.0) yuan, t=4.515, P<0.01). Conclusions Both RDP and LDP are safe and feasible procedures. RDP is more expensive, but RDP is associated with significantly less blood loss and higher spleen-preserving rate, which is more suitable for the non-malignant diseases of pancreatic body and tail with an expectation of splenic preservation.

Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria , which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against . We used glutathione--transferase (GST) pull-down and surface plasmon resonance (SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system.

Objective To explore the clinical effects of laparoscopic combined with open mesh repair for abdominal wall incisional hernia.Methods The retrospective cross-sectional study was conducted.The clinical data of 41 patients with abdominal incisional hernia who were admitted to the Fujian Medical University Union Hospital between September 2011 and June 2017 were collected.All the patients underwent laparoscopic combined with open mesh repair,with the sequence from laparoscopic surgery to open surgery and then to laparoscopic surgery.Observation indicators:(1) intra-and post-operative situations;(2) follow-up situation.Follow-up using outpatient examination and telephone interview was performed to detect postoperative long-term complications and hernia recurrence up to November 2017.Measurement data with normal distribution were represented as (x)±s.Results (1) Intra-and post-operative situations:forty-one patients underwent successful laparoscopic combined with open mesh repair for abdominal wall incisional hernia.Diameter of hernia ring and defect area of abdominal wall were respectively (10±3)cm and (75±34)cm2.Among 41 patients,25 underwent laparoscopic combined with open mesh repair due to tight intestinal adhesion induced difficult laparoscopic separation;16 underwent laparoscopic combined with open mesh repair due to the larger diameter of the hernia ring induced difficulty of closing hernia ring under laparoscope.Operation time,cases with indwelling drainage-tube,time of drainage-tube removal and duration of postoperative hospital stay were respectively (188±71)minutes,33,(14±3)days and (4.5±2.6)days.Of 41 patients,2 with postoperative incomplete intestinal obstruction were cured by symptomatic treatment;2 with incisional infection were cured by antibiotic therapy,irrigation and dressing change.(2) Follow-up situation:41 patients were followed up for (29±17)months.The postoperative chronic pain of 2 patients was occasional and cannot affect the normal life.There was no occurrence of seroma,mesh infection,intestinal fistula,abdominal compartment syndrome and hernia recurrence during the follow-up.Conclusion The laparoscopic combined with open mesh repair has a better clinical effect for patients of incisional hernia with large hernia ring and tight intestinal adhesion,and surgical methods should be chosen seriously according to the condition of the patients in clinical application.

Objective To investigate the clinical efficacy of laparoscopic resection for retroperitoneal tumor via transabdominal approach.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 37 patients with retroperitoneal tumor who underwent laparoscopic resection via transabdominal approach at Fujian Medical University Union Hospital between January 2011 and August 2017 were collected.The surgical approach of resection for retroperitoneal tumor at the left hypochondriac region,left iliac region,right hypochondriac region and right iliac region referred to laparoscopic distal pancreatectomy,laparoscopic left hemicolectomy,laparoscopic pancreatoduodenectomy and laparoscopic right hemicolectomy respectively.Observation indicators:(1) intra-and post-operative recovery situations;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative tumor recurrence,metastasis and survival of patients up to November 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).Results (1) Intra-and post-operative recovery situations:37 patients underwent successfully laparoscopic resection for retroperitoneal tumor via transabdominal approach.Among 37 patients,4 were converted to open surgery,4 were completed surgery with assisted small incision,4 were combined with adjacent organ resection and other 25 underwent totally laparoscopic resection for retroperitoneal tumor.The operation time,volume of intraoperative blood loss,postoperative gastrointestinal recovery time,postoperative drainage-tube removal time and duration of postoperative hospital stay were respectively (181±73) minutes,(160±87) mL,(3.0± 1.0) days,(3.0±2.0) days and (7± 4)days.Of 37 patients,3 with postoperative complications including 2 of chylous fistula and 1 of delayed gastric emptying were improved by symptomatic treatment.There was no perioperative death.(2) Follow-up and survival situations:37 patients were followed up for 3-82 months,with a median time of 30 months.During the follow-up,1 patient with inflammatory myofibroblastic tumor had recurrence at 15 months postoperatively and underwent surgical resection,however,the patient had liver metastasis at 9 months after the second operation and underwent interventional therapy repeatly.One patient with Castleman and 5 with lymphoma underwent regular chemotherapy and achieved disease-free survival.The other patients had disease-free survival.Conclusion Laparoscopic resection for retroperitoneal tumor via transabdominal approach is safe and feasible.

Objective: To explore the clinical efficacy of ear acupuncture plus injection at Zusanli (ST 36) in treating shoulder pain after laparoscopic gynecological surgery, and to observe its effect on cytokines. Methods: Two hundred patients with shoulder pain after laparoscopic gynecological surgery were randomized into two groups based on their visiting sequence, 100 cases each. The observation group was intervened by ear acupuncture plus injection at Zusanli (ST 36), and the control group was intervened by oral administration of Ibuprofen, 10 d as a treatment course. The clinical efficacies of the two groups were compared after 2 treatment courses; the visual analogue scale (VAS), present pain intensity (PPI) and 36-item short-form health survey (SF-36) were measured before and after the treatment;the changes of interleukin (IL)-6 and IL-10 after the treatment were also observed. Results: The VAS and PPI scores were significantly changed after the treatment in both groups (both P<0.01). After the treatment, the VAS score in the observation group was significantly different from that in the control group (P<0.05). The component scores of SF-36 were significantly changed after the treatment in both groups (P<0.01); after the treatment, the scores of physical functioning (PF), bodily pain (BP), social functioning (SF), and mental health (MH) in the observation group were significantly different from those in the control group (all P<0.05). The contents of IL-6 and IL-10 dropped significantly after the intervention in both groups (both P<0.01), and the between-group differences were also statistically significant (both P<0.01). The total effective rate of the observation group was higher than that of the control group (P<0.05). Conclusion: Ear acupuncture plus injection at Zusanli (ST 36) can significantly improve the shoulder pain after laparoscopic gynecological surgery, down-regulate the expressions of IL-6 and IL-10, and boost the recovery.

Objective To compare 6 sub-function scale differences of frontal lobe function rating scale or a Frontal Assessment Battery(FAB)among patients with two subtypes of vascular cognitive impairment(VCI) to provide clues for the distinctive intervention and disease prevention and control of patients with two subtypes.Methods Totally 220 non-dementia vascular cognitive impairment (NDVCI)patients and 68 patients with vascular dementia(VaD)with final diagnosis were selected.The overall function and six sub-function scores were tested by FAB.Analyzing the score difference and probing a progress tendency from NDVCI to VaD were performed.Results The scores of frontal lobe function rating scale were higher in NDVCI(14.0 ± 2.8)than in VaD (9.5±2.0) patients with significant difference(t =29.92,P =0.00).The scales of frontal lobe function rating score of conceptualization ability (t =6.24,P =0.00),intelligence flexibility (t =7.00,P =0.00),antiinterference ability(t =7.21,P =0.00) and attention suppression(t =5.32,P =0.00) were lower in VaD group than in NDVCI group.The conceptualization weight capacity was significantly lower in VaD group than in NDVCI group(0.04 versus 0.32).Conclusions During a transitive process from NDVCI to VaD,it is important to focus on the mutation and deterioration of conceptualization capacity.