Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.

Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective To determine the effect of trunk motion control on knee biomechanics during single-leg landing. Methods Twenty male healthy basketball players were recruited. The kinematics, kinetics parameters and surface electromyogram (EMG) of knee joints under trunk motion control during single-leg landing were studied by using Vicon motion Analysis system, Kistler force platform and Noraxon surface EMG system. Results Compared with natural landing, there were significant differences in flexion angle at initial contact moment, peak flexion angle and peak flexion moment during deeply inspiratory landing and landing with a stick, and a significantly larger flexion angle at initial contact moment, a larger peak flexion angle and smaller peak flexion moment were also found. Compared with natural landing, there was no statistical difference in peak valgus angle and peak valgus moment, as well as EMG activity of hamstrings, quadriceps muscles of the knee during deeply inspiratory landing and landing with a stick. Conclusions Deeply inspiratory landing or landing with a stick reduce the risk of anterior cruciate ligament (ACL) injury, and the results provide the theoretical basis for prevention of ACL injuries in basketball players during landing.

Objective:To investigate the effect and mechanism of Myosin X on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line H1975 in vitro. Methods:Western blot was applied to detect the expression level of Myosin X expression. The H1975 cell line with stable knockout of Myosin X (KO group) and infected with control virus (NC group) were constucted by using CRISPR/Cas9 technique. The knockout efficiency was validated. The radiosensitivity of two cell lines was measured by colony formation assay and single-hit multi-target model. γ-H 2AX focus formation test and RNA sequencing (RNAseq) analysis were employed to identify the regulatory mechanism of the radiosensitivity of lung cancer cell lines mediated by Myosin X. Results:The expression level of Myosin X in the H1975 cells was significantly up-regulated than those in other NSCLC cell lines (all P<0.01). The lentiviral vector of Myosin X sgRNA-Lenti-CRISPR v2 was successfully constructed. After the puromycin screening, H1975 cell lines with complete knockout of Myosin X and control cell lines (NC group) were obtained. Colony formation assay demonstrated that compared with the NC group, the radiosensitivity in the KO group was significantly higher (The D 0 value was decreased from 1.28 Gy to 1.03 Gy, SF 2 decreased from 0.29 to 0.21, and the sensitization ratio was 1.24). The γ-H 2AX focus formation test showed that the number of damage focus formed at 1 h and 6 h after irradiation in the KO group was significantly larger than that in the NC group ( P<0.05. RNAseq analysis indicated that the expression level of ISLR in the KO group was significantly down-regulated than that IN the NC group ( P<0.05). Conclusion:Knockout of Myosin X can increase the radiosensitivity of H1975 cells probably by interfering the repair of DNA double-strand damage and down-regulating the expression level of ISLR.

Objective To study the effect of ankle taping (restriction of ankle varus and plantar flexion) on biomechanical characteristics of the knee during drop landing on the dominant leg. Methods Eighteen amateur athletes performed the dominant-legged drop landing under two different ankle conditions (with or without taping). Vicon three-dimensional (3D) motion capture system, Kistler force plate and Noraxon surface electromyography (sEMG) system were used to collect kinetic, kinematic and sEMG data for statistical analysis. Results Compared with control group, ankle taping significantly increased flexion angle at initial contact and maximum flexion angle, while significantly decreased the maximum valgus angle. Conclusions The restriction of varus and plantar flexion might reduce the risk of anterior cruciate ligament (ACL) injury. The intervention with ankle taping could modify biomechanical parameters of the knee during drop landing. The ankle taping by restriction of ankle varus and plantar flexion may be an effective measure to prevent ACL injury for collegiate athletes.

The laparoscopic vision platform developed from the prototype of candlelight reflector device to HD, 3D and 4K ultra HD, which revolutionized surgery from open surgery to minimally invasive surgery. With the continuous application in gastric cancer surgery, the importance of laparoscopy in radical gastrectomy is gradually recognized. Radical gastrectomy mainly includes lymph node dissection and digestive tract reconstruction. The reconstruction of digestive tract after radical gastrectomy for distal gastric cancer has been a hot topic of discussion and research, which is directly related to the incidence of postoperative complications, nutritional status and quality of life. This paper mainly discusses the Roux-en-Y digestive tract reconstruction of radical gastrectomy for distal gastric cancer with 4K laparoscopic.

Objective To investigate the expressions and the significance among the three markers TGF β1,Survivin and Caspase-3 in intrahepatic bile duct tissues in patients with intrahepatic bile duct stones.Method Total of 130 paraffin section of intrahepatic bile duct tissue were collected at Department of Pathology,The 904th Hospital of Joint Logistic Support Force of PLA from 2013 to 2018.Total of 50 patients with intrahepatic bile duct stones complicated with bile duct strictures (the stenosis group),40 patients with intrahepatic bile duct stones with chronic inflammation (the inflammation group),and 40 patients with normal liver tissues (the normal control group) were included in this study.The expressions of TGF β1,Survivin and Caspase-3 in liver tissues were detected by immunohistochemistry and compared among the 3 groups to find their correlations with the clinicopathological features of the disease of the patients.Results TGF β1 was expressed in 72.0％ of the patients in the stenosis group,37.5％ in the inflammatory group,and 15.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Survivin was expressed in 78.0％ of the patients in the stenosis group,47.5％ in the inflammatory group,and 25.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Caspase-3 was expressed in 10.0％ of the patients in the stenosis group,42.5％ in the inflammatory group,and 75.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05).Within the stenosis group,TGF β1 was negatively correlated with Caspase-3 (r =-0.882,P ＜ 0.05),and positively correlated with Survivin (r =0.889,P ＜ 0.05).Survivin and Caspase-3 were also negatively correlated (r=-0.923,P＜0.05).Conclusion Abnormal expressions of TGF β1,Survivin and Caspase-3 were involved in the formation of intrahepatic bile duct stones associated with bile duct strictures.

Objective: To compare the clinical effects of surgery within and over 48 hours for hip fractures in elderly patients. Methods: From May 2017 to April 2018, 47 patients over 75 years old with hip fracture were operated in our hospital and met with inclusion criteria. The patients were divided into two groups: within 48-hour group and over 48-hour group according to study design. In the within 48-hour group, there were 22 patients including 5 males and 17 females, aged from 76 to 97 years, with an average age of 83.6±5.0 years, and there were 10 femoral neck fractures (3 total hip arthroplasty, 7 hemiarthroplasty) and 12 femoral intertrochanteric fractures (proximal femoral intramedullary nail fixation). There were 25 patients (7 males and 18 females) in the over 48-hour group, aged from 76 to 98 years, with an average age of 83.8±5.8 years, and there were 10 femoral neck fractures (2 total hip arthroplasty, 8 hemiarthroplasty) and 15 femoral intertrochanteric fractures (proximal femoral intramedullary nail fixation). At the end of the follow-up period, the clinical data of the two groups were compared. The differences in the length of stay, cost of stay (excluding implants), postoperative complications within 1 month, hip function score (Harris score) within 1 month and 3 months, and mortality within 3 months and at the end of follow-up were analyzed. Results: Both groups were followed up for 12 to 24 months, with an average of 17.7 months. The hospitalization time (7.9±3.0 d), hospitalization expenses (16 627.5±6 428.8 yuan), the incidence of early complications after operation (59.1%) and Harris score (80.9±8.6) in the within 48-hour group were significantly better than those in the over 48-hour group (12.3±4.1 d, 23 799.0±9 785.3 yuan, 88.0%, 71.1±9.2, respectively). At 3 months after operation, there was no significant difference in Harris score between the two groups (83.9±7.3 in within 48-hour group and 82.3±8.9 in over 48-hour group; t=0.668, P=0.507). Within 3 months, there was no death inwithin 48-hour group, but 2 in over 48-hour group; and 1 in within 48-hour group at the last follow-up. Conclusion Elderly patients with hip fracture benefit significantly from surgery within 48 hours after admission.