Objective This study aimed to evaluate the application of digital impression and resin model technology in removable partial dentures(RPD)for Kennedy classⅠandⅡdentition defects.Methods Patients with Kennedy classⅠorⅡdental defect were selected and grouped in accordance with the following denture production processes:digital impression/resin model/cast cobalt-chromium alloy framework group(group A),digital impression/resin model/laser printed titanium framework group(group B),alginate impression/plaster model/cast cobalt-chromium alloy framework group(group C),and alginate impression/plaster model/laser printed titanium framework group(group D),with 40 cases in each group.The final RPD was examined in place in the mouth,and the evaluation indicators included the retention force of clamp ring,the tightness of connector and base,and the accuracy of occlusion.The evaluation scores of each in-dex were used for analysis on the Kruskal-Wallis rank-sum test.Results No statistically significant difference in the score of each index was found among the four groups in RPD.Conclusion The cast cobalt-chromium alloy and laser-printed titanium framework RPD using digital impression and resin model can meet the clinical restoration requirements of patients with Kennedy classⅠandⅡdentition defects.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

Objective:To investigate the anti-oxidative stress effects of microRNA 125b (miR-125b) on lens epithelial cells (LECs) and its possible mechanism.Methods:Twenty-four anterior capsule specimens were collected from 24 eyes of 24 age-related cataract patients during phacoemulsification and 20 normal anterior capsule specimens were obtained from 20 eyes of 20 donors in Henan Eye Hospital from July 2018 to March 2019 under the approval of a Medical Ethics Committee of Henan Eye Hospital (No.YKYY20193151).The reverse transcription PCR and Western blot assay were employed to detect and compare the relative expression levels of miR-125b and nuclear factor E2-related factor 2 (Nrf2) in different specimens.The human lens epithelial cell line HLEB-3 was divided into control group and oxidative stress model group.The oxidative stress models were established by coculture with different concentrations (100, 200, 400 μmol/L) of H 2O 2 for 24 hours, and the cells were cultured with normal medium without H 2O 2 in the control group.The reactive oxygen species (ROS) content was detected by DCFH-DA fluorescent probe, and the activities of total-antioxidative capability (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as malondialdehyde (MDA) concentration were detected by ELISA, and compared among the groups.The expression levels of miR-125b and Nrf2 were detected by reverse transcription PCR and Western blot assay, respectively.The cells were transfected with miR-125b mimics, miR-125b control and miR-125b inhibitor for 24 hours, respectively, and ROS content was detected by DCFH-DA fluorescent probe and T-AOC, SOD and GSH-Px activities as well as MDA concentration were detected by ELISA and compared among different transfected groups.A dual luciferase reporter assay was used to assess an association between miR-125b and Nrf2.The expression level of Nrf2 protein was detected by Western blot assay and the expression levels of Nrf2 and Keap1 were assayed and located by immunofluorescence double staining. Results:The relative expression levels of miR-125b and Nrf2 in the normal lens anterior capsule specimens were 0.21±0.03 and 0.27±0.06, which were significantly lower than 0.89±0.05 and 0.84±0.12 in the cataract specimens, respectively ( t=15.355, P<0.05; t=18.647, P<0.05).The relative expression levels of miR-125b and Nrf2 were significantly increased in various H 2O 2 treated groups in comparison with the control group and were gradually elevated with the increase of H 2O 2 concentration (all at P<0.05).Compared with the control group, the T-AOC, SOD and GSH-Px activities were reduced, and ROS content and MDA concentration were significantly ascended (all at P<0.05).Compared with the miR-125b control group, the T-AOC, GSH-Px and SOD activities were increased, and ROS content and MDA concentration were decreased in the miR-125b mimics group (all at P<0.05).In addition, the T-AOC, GSH-Px and SOD activities were significantly weakened, and ROS content and MDA concentration were significantly increased in the miR-125b inhibitor group in comparison with the miR-125b control group (all at P<0.05).Dual luciferase reporter assay showed that miR-125b targeted to the expression of Nrf2 in the H 2O 2 model cells.The fluorescence of Nrf2 in the cytoplasm was the strongest with more nuclear transfer in the miR-125b mimics group, and the expression intensity of Keap1 in the cytoplasm was weaker.The expression of Nrf2 was the weakest with less nuclear transfer in the miR-125b inhibitor group, and the expression level of Keap1 in the cytoplasm was stronger. Conclusions:MiR-125b can enhance the anti-oxidative stress of LECs in age-related cataractous eyes probably by upregulating the expression of Nrf2 and activating the Keap1/Nrf2 signaling pathway.

Objective:To evaluate the modified efficacy of thoracic paravertebral block (TPVB) combined with general anesthesia in the patients undergoing laparoscopic radical nephrectomy.Methods:Eighty patients, aged 38-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic radical nephrectomy, were selected and randomly divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group GA) and TPVB combined with general anesthesia group (group TPVB+ GA). A paravertebral catheter was placed at T 8 and T 10 under ultrasound guidance before induction of anesthesia, and 0.5% ropivacaine 10 ml was administered via the catheter in group TPVB+ GA.Anesthesia was induced with propofol, sufentanil, etomidate and rocuronium and maintained by intravenous infusion of propofol and remifentanil.Patient-controlled intravenous analgesia was performed with sufentanil, ketorolac tromethamine and tropisetron at the end of surgery.When postoperative visual analog scale score≥4, tramadol 50 mg was intravenously injected as rescue analgesic.Immediately before anesthesia induction (T 0), at 5 min after establishing pneumoperitoneum (T 1), at 2 h of pneumoperitoneum (T 2), and immediately after the end of pneumoperitoneum (T 3), and at 24 h after operation (T 4), venous blood samples were collected for determination of plasma norepinephrine concentrations (by enzyme-linked immunosorbent assay), plasma cortisol level (using radioimmunoassay), and blood glucose concentrations were measured.The intraoperative consumption of sufentanil and remifentanil was recorded.The intraoperative hypertension, hypotension, and bradycardia were recorded, and the nausea and vomiting, pruritus, and requirement for rescue analgesia occurred within 24 h after surgery were recorded. Results:Compared with group GA, the plasma concentrations of norepinephrine, cortisol and blood glucose were significantly decreased at T 1-4, the intraoperative consumption of sufentanil and remifentanil was reduced, and the postoperative requirement for rescue analgesia was decreased in group TPVB+ GA ( P<0.05). There was no significant difference in the incidence of intraoperative and postoperative adverse reactions between the two groups ( P>0.05). Conclusion:TPVB combined with general anesthesia is helpful in carrying out the anesthetic model of low-consumption opioids and is more helpful in inhibiting intraoperative and postoperative stress responses and postoperative pain responses than general anesthesia alone when used for laparoscopic radical nephrectomy.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .