S OBJECTIVE:To study the effect of roxithromycin on cellular immune function and to study its anti-in-flammatory and immunoregulation effects beside its antibacterial effect.METHODS:The mice were randomized into negative control group,roxithromycin(high,medium,low dosage group)groups and dexamethasone group,the splenic lymphocyte conversion ratio of each group was determined by in vivo method and in vitro method respectively after14days of intragastric administration of drugs.RESULTS:Compared with the negative control group,roxithromycin(high,medium,low dosage)groups could significantly reduce splenic lymphocyte conversion ratio of mice(P

Objective:To investigate the effects of establishment of a trauma center on the therapeutic efficacy for patients with severe multiple injuries.Methods:A retrospective study was conducted in the patients who had been treated at The Second Affiliated Hospital, University of South China for severe multiple injuries from October 2015 to September 2019. They were assigned into 2 groups. The study group included 102 patients who had been treated after establishment of our trauma center (from October 2017 to September 2019) while the control group 126 patients who had been treated before establishment of our trauma center (from October 2015 to September 2017). The 2 groups were compared in terms of time for emergency treatment (from admission to emergency surgery or ICU), ICU stay, hospital stay, total medical costs and mortality.Results:There was a significant difference between the 2 groups in time for emergency treatment [51 (47, 57) min for the study group versus 97 (87, 107) min for the control group] ( P<0.05). There were no significant differences between the 2 groups in ICU stay [4 (1.8, 9.3) d versus 4 (2.0, 10.0) d], hospital stay [25.5 (15.8, 39.0) d versus 21.5 (12.8, 41.5) d], or total medical costs [￥41,259.0 yuan (￥26,950 yuan, ￥81,599 yuan)] ( P>0.05). There was a significant difference between the 2 groups in mortality [12.7% (13/102) for the study group versus 24.6% (31/126) for the control group] ( P<0.05). Conclusion:Establishment of a trauma center can effectively shorten time for emergency treatment, improve treatment efficacy and reduce mortality for patients with severe multiple injuries.

Objective To investigate the efficacy of three-dimensional (3D) printing used to assist the treatment of pilon fracture combined with ipsilateral tibial shaft fracture.Methods From May to July 2016,3 patients with pilon fracture combined with ipsilateral tibial shaft fracture were treated at Department of Traumatic Orthopedics,The Second Affiliated Hospital,University of South China.They were all male,aged from 26 to 47 years.They all had preoperative 3D CT scan.Their CT data were imported to Mimics software for 3D reconstruction.After their fracture 3D models were manufactured by 3D printing,precise patient-specific surgical plans were made to guide their actual operations.Postoperatively,Johner-Wruhs scores were used to evaluate the treatment of tibial shaft fracture,Burwell-Charnley scores to evaluate the treatment of pilon fracture and Tornetta scores to evaluate the therapeutic outcomes.Results All the operations were performed according to the patient-specific surgical plans designed preoperatively.All the fractures achieved bony union without any infection,exposure of bone or internal fixation,osteofascial compartment syndrome or neurovascular injury.The outcomes of tibial shaft fracture were excellent by Johner-Wruhs scoring,anatomic reduction was achieved for pilon fractures by Burwell-Charnley scoring and the therapeutic outcomes were excellent by Tornetta scoring.Conclusion In the treatment of pilon fracture combined with ipsilateral tibial shaft fracture,3D printing can help making of precise and patient-specific surgical plans to promote clinical efficacy.

Objective To explore the effect ofthymosin alpha-1 (Ta1) on postnatal systemic inflammation-induced learning and memory impairment in mice and their relevant mechanism.Methods (1) Twenty-four neonatal C57BL/6 mice were randomly assigned into normal saline group,lipopolysaccharide (LPS,0.3 mg/kg) group,LPS (0.6 mg/kg) group,and LPS (0.9 mg/kg) group.And the animals were intraperitoneally injected with different doses of LPS or equal volume of saline for 5 days.The variations of body weight,liver weight relative to the body and tumor necrosis factor-α (TNF-α) level in serum and brain tissues were observed to determine the appropriate dose of LPS for simulating neonatal clinical infection.(2) A total of 60 newborn mice were randomly divided into three groups:control group,LPS group and Ta1 treatment group;mice in each group were continuously injected with equal volume saline,LPS (0.6 mg/kg) and Tal (0.4 mg/kg)+LPS (0.6 mg/kg) for 5 days.On day 28 and on day 56,Morris water maze was used to measure the spatial learning and memory abilities of mice;the concentrations of TNF-α,interleukin-1β (IL-1β),brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus were examined by ELISA,and the expressions of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were measured by Western blotting.Results (1) As compared with the normal saline group,the mice in the LPS group (0.6 mg/kg) had significantly slower growth ([2.23±0.22] g vs.[1.18±0.21] g),increased relative liver weight to the body (0.052±0.004 vs.0.072±0.007) and increased TNF-α levels in serum and brain tissues ([62.01±3.32] pg/mL vs.[151.06± 14.51] pg/mL;[186.03±13.24] pg/mL vs.[298.71±41.61] pg/mL,P＜0.05).(2) As compared with the LPS group,Tal treatment group had significantly shortened average escape latency in place navigation test,prolonged active time in spatial probe test,statistically decreased hippocampal TNF-α,IL-1β,TLR4 and NF-κB levels ([73.32±5.18] pg/mL vs.[58.61 ±4.03] pg/mL;[99.15±8.30] pg/mL vs.[75.56±6.13] pg/mL;2.32±0.29 vs.1.71±0.26;1.77±0.24 vs.1.26±0.14) and significantly increased BDNF and NGF levels ([1.33±0.12] pg/mL vs.[1.69±0.25] pg/mL;[41.45±3.47] pg/mL vs.[50.38±5.02] pg/mL,P＜0.05).Conclusion Tal improves learning and memory functions and alleviates neuro-inflammation in postnatal infection of mice,and the underlying mechanism probably involves in inhibiting TLR4/NF-κB signaling pathway activation and increasing neurotrophic factors.

Objective:To investigate the effects of a novel retrograde tibial nail (RTN) in the treatment of distal tibial fractures.Methods:A retrospective study was conducted in the 11 patients with distal tibial fracture who had been admitted to Department of Traumatic Orthopedics, The Second Affiliated Hospital, Hengyang Medical School from July 2020 to July 2021. There were 5 male and 6 females, aged from 18 to 70 years (average 54.7 years). By the AO/OTA classification, there were 7 extra-articular distal fractures (3 cases of type 43-A1, 3 cases of type 43-A2 and one type 43-A3) and 4 intra-articular fractures (2 cases of type 43-C1 and 2 cases of type 43-C2); by the Gustilo classification, there were 7 closed fractures and 4 open fractures (2 cases of type I and 2 cases of type Ⅱ). All fractures were fixated with a novel RTN. Deformities like distal tibial varus and valgus as well as fracture-related complications were observed after operation while the curative effects evaluated by the ankle-hindfoot score of the American Orthopaedic Foot and Ankle Society (AOFAS).Results:This cohort was followed up for an average of 7.4 months (from 5 to 12 months). All patients obtained clinical union and recovered daily life and work. Radiographic evaluation showed no distal tibial varus or valgus. There were no such complications as postoperative infection, exposure of bone and internal fixation, compartment syndrome, or neurovascular lesion. According to the ankle-hindfoot score of AOFAS, 7 cases were excellent and 4 cases good.Conclusion:This novel retrograde tibial nail may result in good efficacy in the treatment of distal tibial fracture, but its advantages still need further verification.

Objective:To investigate the effects of calcium sulfate on the proliferation of osteoblast-like MG-63 cells and the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) system.Methods:The extract of calcium sulfate was prepared. The osteoblast-like MG-63 cells were cultured for 24 hours in the medium containing calcium sulfate (the calcium sulfate group) and in the normal medium without calcium sulfate (the blank group), respectively. The growth of osteoblast-like MG-63 cells was observed and their proliferation detected by CCK-8. The mRNA and protein expression levels of OPG/RANKL were detected.Results:The growth of osteoblast-like MG-63 cells was fine in both groups. The CCK-8 test showed that the absorbance value at 24 h was 0.997±0.008 for the calcium sulfate group, significantly higher than that for the blank group (0.640±0.003) ( P<0.001). Respectively, the mRNA expression levels of OPG were 2.834±0.176 and 1.005±0.102 and the mRNA expression levels of RANKL 0.355±0.035 and 1.002±0.068 for the calcium sulfate group and the blank control group, showing statistically significant differences ( P<0.001). The results of Western blot showed that compared with the blank control group, the protein expression of OPG in osteoblast-like MG-63 cells was promoted but the protein expression of RANKL inhibited in the calcium sulfate group. Conclusion:Calcium sulfate may have a positive effect on bone formation, because it can promote the proliferation and activity of osteoblast-like MG-63 cells and regulate the OPG/RANKL/RANK system.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.