Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

Objective To study the characteristics of gait behavior in a mouse model of chronic ankle instability and provide a reference for the study of the mechanism of chronic ankle instability as well as drug screening and evaluation.Methods Thirty C57BL/6J male mice were randomly divided into a control group(n=15)and an injury group(n=15).In the control group,the ankle joint underwent sham operation,and in the injury group,the anterior talofibular ligament and calcaneofibular ligament of the left ankle joint were transected.Gait parameters were analyzed in each group using TreadScan passive gait analysis system.Results Compared with the control group,the injury group showed a 28.43％increase(P＜0.05)in average standing time and a 23.07％increase(P＜0.05)in the percentage of standing time,whereas the average swing time and the percentage of swing time were shortened by 50.63％(P＜0.001)and 19.75％(P＜0.01),respectively.The average braking time and average stride time in the injury group were also shortened by 18.37％(P＜0.01)and 37.86％(P＜0.001),respectively.The injury group exhibited a decrease in step length,anterior-posterior step width,and mediolateral step width by 36.96％,13.66％,and 8.10％,respectively.The total movement speed and instantaneous speed decreased by 8.05％and 11.12％,respectively,while the stride frequency increased by 51.41％.The average footprint area and average maximum standing area decreased by 8.8％and 13.24％,respectively,and foot pressure decreased by only 3％.The plantar pressure distribution in the injury group was uneven,with a more obvious decrease in plantar pressure in the hindfoot,especially a 13.92％decrease in plantar pressure in the right posterior quadrant.Conclusions Mice with chronic ankle instability adopt a more conservative walking pattern during the motion,reducing movement volume and amplitude to improve coordination and stability during walking.

Objective To study the characteristics of gait behavior in a mouse model of chronic ankle instability and provide a reference for the study of the mechanism of chronic ankle instability as well as drug screening and evaluation.Methods Thirty C57BL/6J male mice were randomly divided into a control group(n=15)and an injury group(n=15).In the control group,the ankle joint underwent sham operation,and in the injury group,the anterior talofibular ligament and calcaneofibular ligament of the left ankle joint were transected.Gait parameters were analyzed in each group using TreadScan passive gait analysis system.Results Compared with the control group,the injury group showed a 28.43％increase(P＜0.05)in average standing time and a 23.07％increase(P＜0.05)in the percentage of standing time,whereas the average swing time and the percentage of swing time were shortened by 50.63％(P＜0.001)and 19.75％(P＜0.01),respectively.The average braking time and average stride time in the injury group were also shortened by 18.37％(P＜0.01)and 37.86％(P＜0.001),respectively.The injury group exhibited a decrease in step length,anterior-posterior step width,and mediolateral step width by 36.96％,13.66％,and 8.10％,respectively.The total movement speed and instantaneous speed decreased by 8.05％and 11.12％,respectively,while the stride frequency increased by 51.41％.The average footprint area and average maximum standing area decreased by 8.8％and 13.24％,respectively,and foot pressure decreased by only 3％.The plantar pressure distribution in the injury group was uneven,with a more obvious decrease in plantar pressure in the hindfoot,especially a 13.92％decrease in plantar pressure in the right posterior quadrant.Conclusions Mice with chronic ankle instability adopt a more conservative walking pattern during the motion,reducing movement volume and amplitude to improve coordination and stability during walking.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

Nasal preparations have unique advantages in drug delivery and are widely used in the treatment of local and systemic diseases. Nasal administration of traditional Chinese medicine （TCM） has a long history in China. In recent years， nasal preparations of TCM have attracted wide attention. Based on the information about nasal preparations of TCM from the database of National Medical Products Administration （NMPA）， Yaozh.com and China National Knowledge Internet （CNKI） in the recent 30 years， the formulation， the listed products， commonly used TCM， pharmaceutical excipients， clinical application and safety research of modern nasal preparations of TCM were summarized and expounded. Focusing on many problems in the development of modern nasal preparations of TCM， such as inaccurate dosage of some products， incomplete quality standard system of pharmaceutical excipients， imperfect safety evaluation， lack of research and development of nasal drug delivery devices and so on， the possible solutions and prospects were put forward from the aspects of optimizing the extraction and separation process of TCM， the quality control and application method of pharmaceutical excipients， the development of new dosage forms， the safety evaluation of nasal administration of TCM， and the design and development of nasal administration devices. The aim is to provide ideas for the development of nasal preparations of TCM and provide scientific basis for its sustainable utilization.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

OBJECTIVE: To explore the high risk factors of adult complex appendicitis, and to provide a reference for the development of a reasonable treatment strategy for acute appendicitis. METHODS: A retrospective case-control study was conducted to collect clinical data of 312 adult patients with acute appendicitis confirmed by pathology undergoing appendectomy, including open and laparoscopic surgery, from May 2011 to August 2016 at Affiliated Hospital of Qingdao University. Age <14 years old, pregnant women, complicating abscess around the appendix, AIDS, blood system diseases, autoimmune diseases, inflammatory bowel disease or progressive cancer patients were excluded. According to the intra-operative findings and pathological types, patients were divided into complex appendicitis(112 cases, including gangrene and perforation) and non-complex appendicitis (200 cases, including simple and non-perforated appendicitis, ie suppurative appendicitis). After comparing the clinical data of these two groups, statistically significant variables were induded for multivariate logistic regression analysis to identify risk factors of complex appendicitis, and to establish a regression model. Enter method was applied to establish the regression equation: P=ExpiΣBiXi/1+ExpΣBiXi, and to calculate the relative risk of each variable. Meanwhile, retrospective and prospective verification was performed on this predictive model (cases of acute appendicitis from September 2016 to December 2017 were further collected). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of complex appendicitis were calculated with the regression model. RESULTS: Comparison of the clinical data between the complex appendicitis group and the non-complex appendicitis group showed that differences of 10 preoperative indexes were statistically significant, including period from abdominal pain to admission [(59.1±42.6) hours vs. (47.5±34.4) hours, t=3.051, P=0.002], white blood cell count [(12.9±3.7)×10/L vs. (9.2±4.0)×10/L, t=9.755, P<0.001], neutrophil count [(9.8±4.0)× 10/L vs.(7.1±3.9)×10/L, t=6.020, P<0.001], neutrophil percentage[(84.5±8.7)% vs.(68.2±16.0)%, t=12.754, P<0.001], C-reactive protein levels [(86.0±45.4) μg/L vs. (55.9±35.8) μg/L, t=7.614, P<0.001], serum albumin levels [(334.0±4.8) g/L vs. ( 41.0±4.3) g/L, t=16.055, P<0.001], vomiting ratio [44.6%(50/112) vs. 23.5%(47/200), χ²=14.980, P<0.001], high fever(≥39°C) ratio [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022], the proportion of patients ≥60 years old [22.3%(25/112) vs. 13.0%(26/200), χ²=4.562, P=0.038] and previous history of appendicitis [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022]. The above 10 variables were included in the logistic regression model for multivariate analysis. The results showed that six variables were associated with complex appendicitis. According to their strength, they were old age (≥60 years old) X1(OR=5.094), high fever (≥39°C) X2(OR=4.464), neutrophil count X6 (OR=1.269), neutrophil percentage X4 (OR=1.077), C-reactive protein level X5 (OR=1.027), and serum albumin level X3 (OR=0.763). A predictive regression model was established: P=1/[1+e], whose sensitivity and specificity of judging complex appendicitis were 76.8%(86/112) and 90.0%(180/200),respectively. Sensitivity and specificity for predictive value of complex appendicitis in further prospective validation of the model were 76.2%(48/63) and 81.1% (30/37), respectively. CONCLUSIONS Age ≥ 60 years old, body temperature ≥39°C, increased neutrophil count, neutrophil percentage and C-reactive protein levels, and hypoalbuminemia are risk factors for complex appendicitis. The establishment of predictive model may help determine complex appendicitis.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Appendicitis ; diagnosis ; epidemiology ; pathology ; Case-Control Studies ; Female ; Humans ; Leukocyte Count ; Middle Aged ; Models, Statistical ; Pregnancy ; Retrospective Studies ; Risk Factors

Aim To investigate the role of matrix metalloproteinase-9 down-regulation in the learning and memory dysfunction induced by propofol treatment in rats.Methods 7-day-old SD rats were randomly divided into three groups(n=18):control group(NS group) and repeated doses of propofol group(RP group) was intraperitoneally injected with normal saline and propofol respectively for consecutive seven days, single dose of propofol group(SP group) were intraperitoneally injected with normal saline first for consecutive six days, and then injected with propofol on 7th day.The blood gas and glucose levels were monitored of six rats randomly selected from each group.Morris water maze was conducted to test the learning and memory functions of the remaining rats.The expression of MMP-9, BDNF and caspase-3 was detected by Western blot, and the hippocampal neuron apoptosis was determinated by TUNEL staining.Results Compared with NS group and SP group, the escape latency in RP group was prolonged significantly, exploration time and the number of crossing the platform in RP group were markedly decreased(P<0.05).The expressions of MMP-9 and mBDNF in RP group declined, but the expression of proBDNF and the ratio of proBDNF/mBDNF in RP group were higher than those in NS group and SP group(P<0.05).Compared with NS group and SP group, the number of apoptotic neurons and the expression of cleaved-caspase-3 in RP group were increased significantly, but the expression of pro-Caspase3 in RP group was reduced(P<0.05).There was no difference between SP group and NS group regarding all the results(P>0.05).Conclusions Repeated exposure to propofol can lead to a decline in long-term learning and memory functions in neonatal rats, which may be related to the down-regulation of MMP-9 expression, proBDNF and mBDNF conversion disorder in hippocampus and the apoptosis of hippocampal neurons.However, single exposure to propofol has no significant effect.

Aim To observe the improvement effects of parecoxib on ventricular remodeling after acute myocardial infarction in rats and its influence on PI3K/Akt signaling pathway.Methods Forty male Sprague-Dawley rats were randomly divided into five groups(n=8):sham operation group (group S), ventricular remodeling model group(group R), low dose of parecoxib group(group P1), middle dose of parecoxib group(group P2), and high dose of parecoxib group(group P3).A myocardial infarction model was established by ligating the left anterior descending branch(LAD) of coronary artery in group R, group P1, group P2 and group P3.One day after the operation,the rats were given intraperitoneal injection of 4,8,12 mg·kg-1 parecoxibin Group P1, group P2 and group P3,respectively, for two weeks.The same volume saline was given in group S and group R.Four weeks later, LVSP, LVEDP,+dp/dtmax,-dp/dtmax were monitored.The hearts were harvested to calculate left ventricular hypertrophy index.The pathological change of heart was examined with an optical microscope.The expressions of atrial natriuretic peptide(ANP) mRNA and brain natriuretic peptide(BNP) mRNA were detected by RT-PCR.The expression of PI3K,Akt,P-Akt and caspase-3 was detected by Western blot.Results Compared with group S, the cardiac function was decreased, the left ventricular hypertrophy index, the expression levels of ANP,BNP mRNA, caspase-3 were increased, and the expression levels of PI3K, P-Akt were reduced in group R(all P<0.05).Compared with group R, the cardiac function was ameliorated, the left ventricular hypertrophy index were reduced in group P2 and group P3(all P<0.05).The expression levels of ANP,BNP mRNA, Caspase-3 were decreased, and the expression levels of PI3K and P-Akt were increased in group P1,group P2 and group P3(all P<0.05).Conclusions Middle and high doses of parecoxib can mitigate the process of ventricular remodeling after myocardial infarctionand improve the myocardial function, and its underlying mechanism may be related to activating PI3K/Akt signaling pathway.