Advances in the regulation of autosomal dominant polycystic kidney disease by Hippo signaling pathway / 中华肾脏病杂志

The Hippo signaling pathway is highly conserved in evolution, and participates in the regulation of cell proliferation, differentiation, and tissular dynamic balance, and plays an important role in regulating tissue, organ size, and cell number. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage renal disease. Emerging studies have identified the Hippo signaling pathway is closely related to the occurrence and development of ADPKD. The abnormal activity and expression of the main members of the pathway affect the cilia and cell polarity of renal tubular epithelial cells and induce the formation of renal cysts. The review summarizes the potential mechanism of the Hippo pathway in the pathogenesis of ADPKD, the crosstalk with other signaling pathways, and the variances in different species, and discusses the strategies for the treatment of ADPKD based on the Hippo signaling pathway to provide new strategies for the treatment.

Comparison of therapeutic effects between anatomical reconstruction of the coracoclavicular ligament at the original insertion point and clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation / 中华骨科杂志

Objective:To compare the clinical efficacy of anatomical reconstruction of coracoclavicular ligament at the original insertion point and clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation.Methods:Retrospective analysis was made on the data of 67 patients with acromioclavicular joint dislocation who received surgical treatment in the Department of Orthopaedics of the First Affiliated Hospital of Nanjing Medical University from June 2015 to January 2021. According to the surgical method, they were divided into reconstruction group (using the technique of anatomical reconstruction of coracoclavicular ligament at the original insertion point) and hook plate group (using the clavicular hook plate). There were 37 cases in the reconstruction group, including 26 males and 11 females, aged 47.2±9.6 years (range, 18-65 years), 13 cases on the left and 24 cases on the right. Among the 37 patients, 8 were sports injuries, 14 were falls, 11 were traffic accidents, and 4 were external force injuries. The average time from injury to surgery was 8.3±2.3 days. There were 30 cases in the hook plate group, including 24 males and 6 females, aged 47.4±9.7 years (range, 18-67 years), 12 cases on the left and 18 cases on the right. Among the 30 patients, 7 were sports injuries, 11 were falls, 9 were traffic accidents, and 3 were external force injuries. The average time from injury to surgery was 7.9±2.6 days. The surgical time, incision length, intraoperative bleeding, hospital stay, postoperative coracoclavicular separation ratio, and postoperative complications were compared between the two groups. Constant-Murley score and visual analog scale (VAS) were used to assess the shoulder joint function and pain degree of patients.Results:Both groups of patients were followed up, with a follow-up time of 12.3±0.4 months for the reconstruction group and 12.2±0.5 months for the hook plate group. The operation time (105.8±10.0 min), incision length [12.0 (11.0, 13.0) cm] and hospitalization time (6.8±2.1 d) in the reconstruction group were longer than those in the hook plate group [48.3±4.9 min, 10.0 (10.0, 11.0) cm, and 5.5±2.7 d], while the intraoperative blood loss (75.1±3.9 ml) was less than that in the hook plate group (90.3±6.3 ml), the differences were statistically significant ( P<0.05). The VAS [4.0 (3.0, 5.0), 3.0 (3.0, 3.0), 2.0 (1.0, 2.0) points] and Constant-Murley score (65.4±4.5, 84.9±2.5, 90.1±2.5 points) of the reconstruction group at 3 days, 3 months, and 12 months after surgery were better than those of the hook plate group [5.0 (4.0, 5.0), 4.0 (4.0, 4.0), 3.0 (3.0, 4.0) and 56.9±3.5, 79.6±4.0, 86.8±2.4 points], the difference was statistically significant ( P<0.05). At the last follow-up, there was a statistically significant difference in the separation ratio of coracoclavicular distance between the reconstruction group (0.12±0.08) and the hook plate group 0.22±0.15 ( t=3.25, P=0.002). There was no significant difference ( Z=-0.52, P=0.605) in the separation ratio of acromioclavicular distance [0.16 (0.05, 0.25) and 0.16 (0.04, 0.40)]. In the hook plate group, 6 cases had shoulder joint foreign body sensation and 2 cases had acromioclavicular joint redislocation (both Rockwood type III). Because the shoulder joint function did not affect their daily life, neither patient underwent secondary surgery. And no case of acromioclavicular joint redislocation occurred in the reconstruction group. Conclusion:Compared with the clavicular hook plate fixation, anatomic reconstruction of coracoclavicular ligament at the original insertion point in the treatment of acromioclavicular joint dislocation can reduce the pain of the shoulder joint earlier, which has the characteristics of small trauma, good effect, and reduces the steps of internal fixation removal, and has good clinical curative effect.

More attention for high-risk pathological features for stage Ⅱ colorectal cancer required / 中华病理学杂志

Stage Ⅱ (T3-4N0M0) accounts for 25% of colorectal cancer and five-year survival is between 70% and 80%. However, 25% of patients develop distant metastases and have a survival rate similar to that of stage Ⅲ disease. However, whether or not to give adjuvant chemotherapy is still a controversial issue. As a result, there has been a lot of interest in the identification of the pathological factors underlying the poor prognosis associated with this stage, in order to establish a firmer basis for the administration of adjuvant chemotherapy. But not all high-risk factors are equal for stage Ⅱ colorectal cancer, variability still exists in the management and outcomes of high-risk patients. Here be introduced and commented on thinking and understanding about its controversy and evolution for the attention of the working pathologist and gastroenterologist doctors.

Comparison of coracoclavicular ligament anatomical reconstruction versus clavicular hook plate in treatment of Neer Ⅱb distal clavicular fractures / 中华创伤骨科杂志

Objective:To compare the clinical efficacy between coracoclavicular ligament anatomical reconstruction and clavicular hook plate in the treatment of Neer Ⅱb distal clavicular fractures.Methods:A total of 64 patients with Neer Ⅱb clavicular fracture were treated at Department of Orthopaedics, The First Affiliated Hospital to Nanjing Medical University from September 2016 to June 2019. They were 35 males and 29 females, aged from 19 to 68 years (average, 50.7 years). They were assigned into 2 groups according to their operative methods: a reconstruction group of 30 cases undergoing coracoclavicular ligament anatomical reconstruction and a hook plate group of 34 cases undergoing fixation with a clavicular hook plate. The 2 groups were compared in terms of hospital stay, operation time, intraoperative blood loss, surgical incision length, postoperative coracoclavicular separation ratio, visual analogue scale (VAS) and Constant-Murley shoulder scores at 3, 6 and 12 months after operation, and postoperative complications.Results:There was no significant difference in general data between the 2 groups, showing comparability between groups ( P>0.05). Operations were completed uneventfully and surgical incisions healed by primary intention in both groups after operation. All the patients were followed up for 12 to 24 months (average, 14.6 months). The operation time [(74.6±22.0) min] and incision length [(10.4±0.4) cm] were significantly shorter but the intraoperative blood loss [(90.2±5.3) mL] was significantly less in the hook plate group than those in the reconstruction group [(95.6±20.8) min, (12.4±0.9) cm and (74.2±3.5) mL] ( P<0.05). There was no significant difference in hospital stay between the 2 groups ( P>0.05). At 3, 6 and 12 months after operation, the VAS scores (1.8±0.5, 1.2±0.3 and 1.1±0.2) and Constant-Murley scores (85.2±4.6, 91.1±2.6 and 92.1±2.2) in the reconstruction group were significantly better than those in the hook plate group (3.2±1.0, 1.6±0.3 and 1.5±0.3; 73.6±2.9, 85.9±4.6 and 87.0±3.1) ( P<0.05). At the last follow-up, the postoperative coracoclavicular separation ratio (elevation) in the hook plate group (0.20±0.16) was significantly greater than that in the reconstruction group (0.10±0.05) ( P<0.05). Conclusion:In the treatment of Neer ⅡB distal clavicular fractures, coracoclavicular ligament anatomical reconstruction may lead to better fixation and fewer postoperative complications than a clavicular hook plate, demonstrating fine clinical efficacy.

Epidural block associated with improved long-term survival after surgery for colorectal cancer: A retrospective cohort study with propensity score matching / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of epidural anesthesia on the long-term prognosis of patients after selective colorectal cancer resection surgery.@*METHODS@#This was a retrospective cohort study and approved by local institution review board. Patients who underwent selective colorectal cancer resection surgery from August 2011 to December 2012 in Peking University First Hospital were enrolled. The patients were divided into general anesthesia (GA) group and combined epidural-general anesthesia (EGA) group according to anesthesia type. Primary outcome was patient's long-term survival status. Secondary outcome included the overall incidence of in-hospital complications and length of postoperative in-hospital stay. Propensity score was used to match cases between the two groups based on the probability of receiving EGA. Survival was analyzed by Kaplan-Meier analysis and compared by Log-rank test between the two groups. Multivariate Cox regression analysis was used to investigate the relationship between epidural anesthesia and other variables with long-term survival status.@*RESULTS@#A total of 264 patients were entered into final analysis, including 166 cases in GA group and 98 cases in EGA group. Mean age of the patients was (63.3±12.1) years and mean survival time was 47.2 (95%CI 45.7-48.7) months. Before the propensity score match, the mortality in EGA group was 16.9% (28/166) and 9.2% (9/98) in GA group. But comparison between the two groups had no statistical significance (P=0.091). After the propensity score match, 87 paired cases were matched and analyzed. The risk of long-term mortality in EGA group was lower than that of GA group by Kaplan-Meier analysis (5.7% vs.16.1%, HR=0.344, 95%CI 0.124-0.955, P=0.041). Mean survival time of EGA group was longer than that of GA group (50.3 months vs. 42.9 months, P=0.032). Multivariate Cox regression ana-lysis showed that EGA, in comparison with GA, was related with lower risk of long-term mortality (HR=0.326, 95%CI 0.117-0.909, P=0.032). Age (HR=1.042, 95%CI 1.001-1.085, P=0.046) and preoperative lymph node metastasis (HR=2.924, 95%CI 1.162-7.356, P=0.023) were also related with increased risk of long-term mortality.@*CONCLUSION@#Present study found that perioperative use of epidural anesthesia and analgesia was associated with improvement of the patient's long-term survival. Well-designed studies are needed to verify this hypothesis.

Vitamin D regulates cell viability, migration and proliferation by suppressing galectin-3 (Gal-3) gene in ovarian cancer cells

Vitamin D deficiency is identified as a risk factor for the occurrence and recurrence of ovarian cancer.Galectin-3 (Gal-3) participates in many physiological and pathological processes. In present study, serumvitamin D level was detected using chemiluminescence enzyme immunoassay. Gal-3 expression wasexamined using real-time polymerase chain reaction (PCR), Western blot and immunocytochemistry analysis. SKOV3 cells viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, the migrationof SKOV3 cells was detected using transwell assay, and the proliferation of SKOV3 cells was measured by3H-thymidine incorporation (3H-TdR). Our study demonstrated that vitamin D levels were lower in 40ovarian cancer patients: vitamin D deficiency is closely related to the pathogenesis of ovarian cancer.Treatment with vitamin D reduced the migration and proliferation of ovarian cancer cells. Gal-3 wasoverexpressed in ovarian cancer, which could induce the viability, migration and proliferation ability ofovarian cancer cells, and these effects were abrogated by vitamin D downregulating the expression of Gal-3gene. Therefore, our results support that vitamin D may suppress Gal-3-induced viability, migration andproliferation ability of ovarian cancer cells, which suggests that the use of vitamin D may have beneficialeffects in preventing and treating ovarian cancer.

Role and mechanism of C3a-C3a receptor in autosomal dominant polycystic kidney disease / 中华肾脏病杂志

Objective:To explore the role and mechanism of C3a-C3a receptor (C3aR) in the progression of autosomal dominant polycystic kidney disease (ADPKD).Methods:Renal tissues of ADPKD patients and PKD1 knockout mice were collected. Then the expression of C3a-C3aR, Ki67 and F4/80 in renal tissues was observed. Macrophages were stimulated with lipopolysaccharide (LPS) and interleukin 4 respectively. The expression of C3aR, TNF-α, typing markers and related signal pathway proteins was detected in each group. PKD1 knockout mice were treated with C3aR inhibitor SB290157 (1 mg/kg). Renal pathology, cyst-related indicators and renal function were observed. Results:The expression of C3a and C3aR in ADPKD was up-regulated (both P<0.05); C3aR and F4/80 were co-located in the kidney of polycystic kidney disease (PKD) mice, indicating that C3aR was mainly expressed on membrane of macrophages. In vitro, the expression of C3aR was up-regulated in M1 macrophages ( P<0.05). After the stimulation of C3a, the expression of iNOS, TNF-α and IL-6 mRNA in M1 macrophages were up-regulated (all P<0.05), as well as the secretion of TNF-α, indicating that C3a not only affected the expression of inflammatory factors of M1 macrophages, but also affected the inflammatory microenvironment. In addition, C3a significantly activated Akt in M1 macrophages ( P<0.05). Compared with the control group, the treatment group showed a decrease in C3a-C3aR as well as serum BUN, Scr, cyst index, and two kidneys weight/body weight (2KW/BW) (all P<0.05), and ADPKD related pathway protein expression such as p-ERK and p-P65 was significantly down-regulated (all P<0.05). Conclusions:The increased C3a in polycystic kidney tissue causes infiltration and activation of macrophages through C3aR, and then promotes ADPKD progression. The mechanism may be mediated by Akt activation and increased TNF-α production. C3aR antagonist is a potential research direction in the treatment of ADPKD.

Scientific connotation of "the older, the better" for long term-stored Chinese materia medica / 中草药

Long term-stored method is characteristic for process of Chinese materia medica. Exposed to physical, chemical, and biological factor from surrounding environment during long term-stored, Chinese materia medica became moderate in property, stronger in efficacy and less toxicity, conducing to improvement of safety, effectiveness and quality stability in clinical application. Based on the herbal literature and modern research, the variation of physical property, chemical compounds and efficacy of Chinese materia medica after the long term-stored were systematically summarized, and the mechanism was discussed, in order to provide research ideas and scientific basis for studying long term-stored method for Chinese materia medica.

Visits of fever clinic during the epidemic of coronavirus disease 2019: A preliminary analysis / 第二军医大学学报

Objective To observe the visits of fever clinic during the epidemic of coronavirus disease 2019 (COVID-19) and the epidemic characteristics of COVID-19, so as to analyze the disease development trend. Methods The clinical data of fever outpatients (including COVID-19 patients) in Gongli Hospital affiliated to Naval Medical University (Second Military Medical University) from Jan. 15, 2020 to Feb. 29, 2020 were collected for epidemiological descriptive analysis. Results Among the 2 193 patients visiting our hospital between Jan. 15, 2020 and Feb. 29, 2020, 97.08% had respiratory system infection, followed by digestive system infection and urinary system infection. Eighty-one suspected cases and 10 confirmed cases of COVID-19 were identified. Among the suspected cases, there were 38 males (46.91%) and 43 females (53.09%). Among the confirmed cases, four were males and six were females. The onset age of the suspected cases ranged from 20 to 69 years old (83.95%), and all the 10 confirmed patients were ≥50 years old. The suspected patients were mainly employees (31 cases, 38.27%) and retirees (14 cases, 17.28%). Among the 10 confirmed patients, eight cases were retirees. Of the suspected cases, 15 (18.52%) had lived in Hubei province and 52 (64.20%) had an epidemiological history. Of the confirmed cases, seven had lived in Hubei province and all had an epidemiological histories. The onset cycles of suspected and confirmed cases were mainly from Jan. 21, 2020 to Feb. 10, 2020. The main clinical symptoms of the suspected cases were fever (66 cases, 81.48%) and cough (50 cases, 61.73%). The blood routine showed normal white blood cell (65 cases, 80.25%), normal lymphocyte (49 cases, 60.49%) and decreased lymphocyte (24 cases, 29.63%). Chest CT showed COVID-19 characteristics in 13 cases (16.05%). Among the 10 confirmed patients, the main clinical manifestations were also fever (nine cases) and cough (eight cases). The blood routine showed normal white blood cells (10 cases), normal lymphocytes (six cases) and decreased lymphocytes (four cases). Chest CT showed COVID-19 characteristics in seven cases. Conclusion COVID-19 is more common in middle-aged and elderly retirees, with significant epidemiological and family clustering characteristics.

Truly anatomic double Endobutton reconstruction of coracoclavicular ligament for acute acromioclavicular joint dislocation of Rockwood type Ⅴ / 中华创伤骨科杂志

Objective To investigate the therapeutic efficacy of truly anatomic reconstruction of the coracoclavicular ligament with two Endobutton devices for acute acromioclavicular joint dislocation of Rock-wood type Ⅴ.Methods From May 2013 to October 2015,25 patients with acromioclavicular joint dislocation of Rockwood type Ⅴ underwent truly anatomic reconstruction of the coracoclavicular ligament using two Endobutton devices.They were 15 men and 10 women,from 18 to 67 years of age (mean,43.0 years).All the dislocations were unilateral,involving 14 left and 11 right sides.The visual analog scale (VAS) and the Constant scoring were used at 3,6,12,18 and 24 months postoperatively for assessments of pain and shoulder function.The coracoclavicular distances on the healthy and affected sides were measured on their anteroposterior X-ray films of bilateral shoulders.Results The 25 patients were followed up for 24 to 48 months (mean,34.0 months).Their VAS score were decreased significantly from preoperative 5.0 ± 0.9 points to 0 ±0.5 points at 24 months after surgery,their Constant score increased significantly from preoperative 45.0 ± 5.6 points to 95.0 ± 2.9 points at 24 months after surgery,and their coracoclavicular distances at the affected side restored significantly from preoperative 23.0± 5.4 mm to 8.0 ± 0.9 mm at 24 months after surgery (all P ＜ 0.05).There was no significant difference in the coracoclavicular distance between the affected and the healthy sides at 24 months after surgery (P ＞ 0.05).No serious complications like acromioclavicular joint re-dislocation or clavicular condylar fracture occurred in any patient.Conclusions Truly anatomic double Endobutton reconstruction of the coracoclavicular ligament is a safe,reliable and creative surgical technique that may yield good to excellent clinical and radiological outcomes in the treatment of acute acromioclavicular joint dislocation of Rockwood type Ⅴ.

Epidemiologic characteristics of fall in the elderly in urban and rural areas in Shanghai / 中华流行病学杂志

Objective@#To understand the epidemiologic characteristics of fall in the elderly in Shanghai, as well as the differences between urban and rural areas, and provide evidence for targeted fall prevention and intervention.@*Methods@#From January to March in 2017, a questionnaire survey was conducted in the elderly aged 60 or above selected from 7 urban communities and 6 rural communities in Shanghai to understand the epidemiologic characteristics of fall in the elderly and analyze the gender and urban-rural differences.@*Results@#In urban area, a total of 3 386 elderly people were surveyed, in whom 441 (13.0%) had fall and 261 (7.7%) were injured after fall. In rural area, a total of 2 826 elderly people were surveyed, in whom 320 (11.3%) had fall and 169 (6.0%) were injured after fall. Fall risk in women were higher than that in men in both urban and rural areas with OR of 1.62 (95%CI: 1.42-1.86) and 1.16 (95%CI: 1.38-1.98) respectively, but the differences of fall related injury were not significant. Compared with urban areas, fall risk and fall related injury risk were both lower in rural areas with OR of 0.86 (95%CI: 0.73-0.99) and 0.74 (95%CI: 0.56-0.99). Compared with urban areas, men had lower risk for fall, and women had lower risk for fall related injury with OR of 0.68 (95%CI: 0.51-0.90) and 0.66 (95%CI: 0.47-0.93) respectively. Fall mainly occurred at home. Fall in urban area more frequently occurred on stairs, and fall in rural area more frequently occurred during farming. More than 60% of the falls had environmental risk factors. Slippery ground and uneven ground were main reasons. The incidence of fracture resulted from fall was high indicated by 89 fracture cases in urban areas (28.2%) and 64 fracture cases in rural areas (36.1%).@*Conclusions@#The risk for fall in Shanghai had gender and urban-rural differences. Targeted intervention should be conducted according to the characteristics of fall in the elderly.

Fear memory and heart rate and blood pressure during conditioned fear in rats with hippocampal lesion or fimbria-fornix transection / 中华行为医学与脑科学杂志

Objective To investigate the effects of dorsal hippocampal lesions (DH) or fimbria-fornix transection (FF) on the learning and memory of conditioned fear and the heart rate and blood pressure in rats.Methods Nineteen male adult Wistar rats were used in this experiment.They were implanted telemetry sensors in their abdominal aortas.Two week later,six of the rats were subjected to permanent NMDA-induced neurotoxic lesions to the dorsal hippocampus (DH) and seven for the fimbria-fornix transection (FF)through stereotactic brain surgery,the left six were treated with saline as the control (Sham).All rats were subjected to a conditioned fear experiment.Meanwhile,changes in heart rate and blood pressure were measured.Results There was no significant difference in heart rate and blood pressure among the rats with the hippocampal operation or fimbria-fornix transection.In the acquisition of conditioned fear,there were significant difference in freezing time among the three group in both inter-trial-interval (ITI) and conditioned stimulus (CS) process (all P＜0.05).The freezing time of the FF group showed significantly lower than that of the Sham group (P＜0.05).There was no significant difference in heart rate and blood pressure among the three group(P＞0.05).In the test of conditioned contextual fear memory,the freezing time percentage in the FF group ((0.31±0.16) ％) significantly lower than that in the Sham group ((2.78± 1.23) ％) (P＜0.05)at the first 3 min of the test.There was a significant difference in heart rate among the three group.The heart rate of FF group ((436.42± 10.16) times/min) was significantly lower than that of the Sham group ((472.48±4.43) times/min,P＜0.01) and the DH group ((469.94 ±7.36)times/min,P＜0.01).In the test of conditioned tone fear memory.The freezing time percentage in FF group ((18.78±6.29) ％) was significantly lower than that in the Sham ((51.77±9.33)％,P＜0.01) and DH group ((59.19±8.13)％,P＜0.01),but the freezing time percentage between the later two groups had no difference (P=0.52).The synchronous telemetry measurement showed there was no significant difference both in the heart rate and the blood pressure among the groups (all P＞0.05) during the conditioned tone test.Conclusion The dorsal hippocampal lesions and fimbria-fornix transection in rats can significantly reduce the learning and memory ability in conditioned fear and scene fear in rats,and the effect of fimbria-fornix transection is more obvious.The decrease in,fear memory is not synchronously reflected in heart rate and blood pressure in rats.

Curcumin Inhibits Lipopolysaccharide-Induced Mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2 / 中华医学杂志(英文版)

<p><b>Background</b>Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro.</p><p><b>Methods</b>For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 μg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared.</p><p><b>Results</b>CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = -6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue.</p><p><b>Conclusion</b>CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.</p>

Correlation of plasma heme oxygenase-1 level and type 2 diabetes mellitus / 中国生化药物杂志

Objective To investigate the correlation of plasma heme oxygenase-1 (HO-1) level and type 2 diabetes mellitus (T2DM). Methods The outpatient with type 2 diabetes mellitus (T2DM) undergoing oral glucose tolerance test and healthy individuals with physical examination were divided into T2DM group and healthy control group, the differences between the two groups in HO-1 and methane dicarboxylic aldehyde (MDA), mean fluorescence intensity (MFI), homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were comparatively analysed , and analyzed the correlations between HO-1 and reactive oxygen species (ROS) MFI, MDA, HOMA-IR and FBG. Results The type 2 diabetes group in MDA and MFI, the expression rate of HO-1 were higher than those of control group (P<0.05), correlation analysis of expression of HO-1 was positively correlated with MFI, MDA (r=0.489, 0.763, P<0.05) in the T2DM group, HO-1, HOMA-IR and FBG were significantly higher than the healthy control group, the difference was statistically significant(P<0.05). The expression of HO-1 and HOMA-IR and FPG levels were positively correlated in the T2DM group (r=0.271, 0.426, P <0.05). Conclusion T2DM patients with hyperglycemia and oxidative stress, plasma HO-1 expression is significantly increased, HO-1 is related to oxidative stress, insulin resistance and hyperglycaemia, which has certain value on clinical assessment of T2DM and therapeutic efficacy.

Effect of Cervical Rotatory Manipulation on Displacement and Intra-stress of Cervical Disc in Different Positions / 中国康复理论与实践

Objective To simulate the cervical rotatory manipulation(CRM)in flexion,neutral and extension positions using three-di-mensional finite element,so as to investigate the effect of this manipulation on the displacement and intra-stress of cervical disc in different positions.Methods By using the method of reverse engineering with Mimics 10.01,Geomagic Studio and Solidworks 14.0,a three-dimen-sional geometric CAD model of C5-6was developed from the CT scan images of a normal adult female aged 25 years.The model was import-ed into Ansys Workbench 14.5,and a three-dimensional finite element model was verified and simulated the CRM.The CRM was decom-posed by principium of manipulation in flexion,neutral and extension,respectively.The parameter of mechanics was analyzed with the fi-nite element system.The change of displacement and intra-stress distribution in cervical disc simultaneous were displayed during simulating the manipulation.Results The posterior part of opposite rotary side of annulus fibers was all retracted,and the displacement was toward an-terior,maximal in flexion position,followed as neutral position and minimal in extension position.In the meantime,the posterior part of the rotary side of annulus fibers was expanded into posterior,minimal in flexion position,followed as neutral position and maximal in extension position.The intra-stress in cervical disc was focused on posterior part of opposite rotary side,opposite rotary side and posterior part of the rotary side in flexion position,neutral position and extension position,respectively,maximal in flexion position,followed as extension posi-tion and minimal in neutral position. Conclusion To treat with cervical spondylotic radiculopathy in the perspective of safety of cervical disc,the CRM should rotate to the unaffected side,first in neutral position,second in flexion position if with poor efficacy.Patients with cer-vical spinal stenosis should not be treated with the CRM.

CREB-regulated transcription coactivator 1: important roles in neurodegenerative disorders / 生理学报

The cAMP-responsive element binding protein (CREB)-regulated transcription coactivator, CRTC (also known as transducer of regulated CREB, TORC), is identified as a potent modulator of cAMP response element (CRE)-driven gene transcription. The CRTC family consists of three members (CRTC1-3), among which the CRTC1 shows the highest expression in the brain. Several studies have demonstrated that the CRTC1 plays critical roles in neuronal dendritic growth, long-term synaptic plasticity, memory consolidation and reconsolidation etc., whereas dysfunction of CRTC1 is mainly involved in neurodegenerative disorders. In light of these findings, we aim to review recent research reports that indicate the CRTC1 dysfunction and its underlying mechanisms in the neurodegenerative disorders.

Analysis of prognostic parameters in patients with breast cancer of size smaller than or equal to 2 cm / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the prognostic parameters in patients with breast cancer of size smaller than or equal to 2 cm which are useful for treatment and follow-up.</p><p><b>METHODS</b>Four hundred and seventy-five patients with breast cancer of size smaller than or equal to 2 cm diagnosed and treated in Affiliated Union Hospital, Fujian Medical University, China during the period from January, 2002 to December, 2008 were enrolled into the study. The clinical features, pathologic findings and follow-up data were analyzed. Kaplan-Meier curve method and Cox proportional hazard regression model were used to study factors which influenced disease-free survival and overall survival of the patients.</p><p><b>RESULTS</b>Onset below 40 years of age (P=0.000), presence of axillary lymph node metastasis (P=0.000) and histologic grade 3 (P=0.013) negatively correlated with 5-year disease-free survival. Onset below 40 years of age (P=0.000), presence of axillary lymph node metastasis (P=0.000), histologic grade 3 (P=0.012) and negative estrogen receptor status (P=0.035) negatively correlated with 5-year overall survival. Multivariate analysis indicated that onset below 40 years of age (HR=3.249, 95% CI: 1.514-6.974, P=0.002) and presence of axillary lymph node metastasis (HR=3.177, 95% CI: 1.695-5.953, P=0.000) were independent predictors of 5-year disease-free survival. Onset below 40 years of age (HR=5.006, 95% CI: 2.013-12.449, P=0.001), presence of axillary lymph node metastasis (HR=4.461, 95% CI: 1.948-10.218, P=0.000) and negative estrogen receptor status (HR=2.612, 95% CI: 1.092-6.246, P=0.031) were independent predictors of 5-year overall survival.</p><p><b>CONCLUSIONS</b>Onset below 40 years of age, presence of axillary lymph node metastasis and negative estrogen receptor status are prognostic indicators in patients with breast cancer of size less than or equal to 2 cm. Assessment of these prognostic parameters would be helpful in treatment and follow-up of this group of breast cancer patients.</p>

Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

A retrospective comparison of the modified tension band technique and the parallel titanium cannulated lag screw technique in transverse patella fracture / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To compare efficacy between the modified tension band technique and the parallel titanium cannulated lag screw technique for the transverse patella fracture.</p><p><b>METHODS</b>Seventy-two patients were retrospectively analyzed aged 22 to 79 years (mean, 55.6 years) with transverse patella fractures, among whom 37 patients underwent the modified tension band and 35 patients received the titanium cannulated lag screw. Patients were followed up for 1-3 years. We analyzed the difference of operation time, complications, fracture reduction, fracture healing time, and the Iowa score for knee function between both groups.</p><p><b>RESULTS</b>In modified tension band group, five patients had skin irritation and seven suffered wire migration, two of whom required a second operation. In comparison, there were no complications in the titanium cannulated lag screw group, which also had a higher fracture reduction rate and less operation time.</p><p><b>CONCLUSION</b>The parallel titanium cannulated lag screw technique has superior results and should be considered as an alternative method to treat transverse patella fracture.</p>

Extracorporeal shockwaves induce osteogenic differentiation of human mesenchymal stem cells by ATP release / 医用生物力学

Objective To investigate whether extracorporeal shockwave could induce differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells by ATP release and the activation of P2X7 receptors. Methods Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and calcium nodule formation. The mRNA expression of P2X7 receptors was determined with real-time RT-PCR. P2X7-siRNA, apyrase, and P2 receptor antagonists were used to evaluate the roles of ATP release and P2X7 receptors in shockwave-induced osteogenic hMSCs differentiation. Results Shockwave treatment released significant amounts of ATP from hMSCs. Shockwaves and exogenous ATP induced hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists prevented osteogenic differentiation of hMSCs. Conclusions Shockwaves can contribute to osteogenic differentiation of hMSCs by realeasing cellular ATP that activate signaling. These research findings provide the theoretical basis for shockwave therapy in treating fracture healing and bone nonunion.