[Analysis of changes in intrinsic neural timescales in male smoking addicts based on whole brain resting-state functional magnetic resonance imaging].

Objective: To investigate the abnormal changes of intrinsic neural time scale (INT) in male smoking addicts based on whole brain resting state functional magnetic resonance imaging (rs-fMRI). Methods: A case-control study. The clinical data and whole brain rs-fMRI data of 139 male subjects, aged (34.1±8.8) years, recruited through the online platform from January 2019 to December 2021 were retrospectively analyzed. According to the existence of smoking addiction, they were divided into smoking addiction group (n=83) and healthy control group (n=56).INT was calculated to reflect the brain neural activity dynamics. Single sample t test was used to obtain the whole brain spatial distribution maps of INT in smoking addiction group and the control group. Then two-sample t test was conducted to explore the difference of INT between the smoking addition group and the healthy control group, with age and years of education as covariates. Finally, Spearman correlation analysis was used to explore the relationship between INT and nicotine dependence scale score and smoking index. Results: Subjects with smoking addiction and healthy control group showed a similar pattern of hierarchical neural timescales, namely shorter INT in sensorimotor areas and longer INT in parietal lobe, posterior cingulate cortex. In addition, in the smoking addiction group, the left medial occipital gyrus (peak t=-3.18), left suproccipital gyrus (peak t=-3.66), bilateral pericalar cleft cortex (left: peak t=-3.02, right: peak t=-3.22), bilateral lingual gyrus (left: peak t=-3.10, right: t peak=-3.04), left cuneus (peak t=-2.97), default network associated brain region [left anterior cuneus(peak t=-3.23), left angular gyrus (peak t=-3.07), and left posterior cingulate cortex (peak t=-3.54) were significantly lower than those of healthy controls (gaussian random field correction, voxel level all P<0.005, mass level all P<0.05). However, there was no significant correlation between INT and nicotine dependence scale score and smoking index (both P>0.05 after Bonferroni correction). Conclusion: Compared with healthy controls, smoking addicts showed abnormal changes in the dynamics of neural activity in the visual cortex and the default network.

[Interpretation of expert consensus for progressive collapsing foot deformity].

Adult flatfoot is a common foot deformity, mainly manifested as medial arch collapsing, hindfoot valgus and forefoot abduction. People have a more thorough understanding of the pathological changes and pathogenesis of flatfoot with further research. There is a new expert consensus for adult flatfoot published in Foot & Ankle Inter. in 2020. The expert panel reviewed the latest literature to develop consensus recommendations for flatfoot, including its nomenclature, diagnosis, classification and operative treatment. The consensus represents a new understanding of the disease and a new concept because of the authority of its authors and the comprehensiveness of its content, and it is also a phased summary of the theoretical and clinical progress of adult flatfoot. This article gives a detailed interpretation of the content in the consensus.

[Correlation between first tarsometatarsal joint sagittal mobility and hallux valgus combined with transfer metatarsalgia].

Objective: To investigate the correlation between the first tarsometatarsal joint (TMT1) sagittal mobility and hallux valgus (HV) combined with transfer metatarsalgia (TM). Methods: The weight-bearing CT (WBCT) imaging data of 111 HV patients (167 feet) who were treated at the Foot and Ankle Surgery Center, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2018 to January 2020 were retrospectively analyzed. The patients underwent PedCAT WBCT scans of both feet, and the hallux valgus angle (HVA), intermetatarsal angle (IMA), plantar distance (PD), medial cuneiform-first metatarsal angle (CMA) and metatarsal protrusion distance (MPD) were measured using CubeVue software. PD and CMA were signs of TMT1 instability. Visual analogue scale (VAS) and foot and ankle ability measures (FAAM) scores were obtained. The patients were divided into TM group and non-TM group according to the presence of metatarsalgia. The TM group and the non-TM group were compared in terms of HVA, IMA, PD, CMA, MPD, VAS and FAAM. Correlations between PD, CMA and HVA, IMA, VAS, FAAM were analyzed using Spearman correlation. Results: Total of 111 cases were included in this study, there were 35 males and 76 females with a mean age of (57.7±14.1) years. The average values of HVA (37.9°±8.6°), IMA (17.9°±2.6°), CMA (2.1°±0.3°) and PD [(1.8±0.4) mm] in TM group were all significantly higher than those in the non-TM group [HVA (32.5°±9.1°), IMA (15.1°±3.4°), CMA (1.7°±0.3°) and PD (1.6±0.2) mm] (All P<0.001). There was no significant difference in MPD between the two groups (P=0.580). The TM group demonstrated a higher VAS score when compared with the non-TM group (P<0.001). The FAAM score of the TM group (54.1±11.8) was significantly lower than that in the non-TM group (66.2±11.4) (P<0.001). The results of Spearman correlation analysis showed that there was no correlation between PD and HVA, IMA and VAS score. There was a negative correlation between PD, CMA and FAAM score, and the difference was statistically significant (rs=-0.637, -0.254, both P<0.001); CMA was positively correlated with HVA, IMA, and VAS score (rs=0.603, 0.971, 0.269, all P<0.001). Conclusions: WBCT is helpful for the diagnosis of TMT1 sagittal instability. The severity of TMT1 sagittal instability is positively correlated with hallux valgus and TM. The TMT1 instability may play an important role in the pathogenesis of hallux valgus.

[Clinical outcomes of anterior tibial tendon transfer combined with supramalleolar osteotomy in stage 3b of varus ankle osteoarthritis].

To investigate the clinical and radiographic results of anterior tibial tendon (ATT) transfer combined with supramalleolar osteotomy in stage 3b of varus ankle osteoarthritis. Totally 13 patients with stage 3b of varus ankle osteoarthritis who received ATT transfer combined with supramalleolar osteotomy in Beijing Tongren Hospital from January 2018 to May 2021 were recruited. There were 6 males and 7 females with a mean age of (57.8±9.3) years. The overall evaluations included the preoperatively and postoperatively radiographic alignments, visual analog scale (VAS) score, and the American Orthopaedic Foot & Ankle Society (AOFAS) clinical ankle-hindfoot scale. The mean follow-up period was (33.5±13.4) months. The tibial articular surface (TAS), talar tilt (TT), and foot and ankle offset (FAO) changed from 83.3°±2.4° to 92.8°±1.7°, 12.3°±4.5° to 7.0°±4.7°, and -7.4%±2.8% to -0.7%±2.2% after the operation, respectively (all P<0.001). The AOFAS and VAS score improved significantly at the final follow-up when compared with those before the operation (both P<0.001). It indicated that ATT transfer after supramalleolar osteotomy can achieve good clinical and radiographic results in the treatment of varus ankle arthritis in Takakura stage 3b.

[Comparation of outcomes of iliac crest bone graft and accessory navicular bone graft in the Cotton osteotomy for pediatric and adolescent flexible flatfoot].

Objective: To compare the outcomes between iliac crest and accessory navicular as different bone grafts in the Cotton osteotomy in the treatment of pediatric flexible flatfoot deformity. Methods: A retrospective cohort study. The clinical data of pediatric flexible flatfoot patients with symptomatic accessory navicular received operations from July 2018 to March 2022 in Beijing Tongren Hospital were retrospectively analyzed. All the patients were treated with Cotton osteotomy. According to the different sources of bone grafting in Cotton osteotomy, the patients were divided into iliac crest group and accessory navicular group. There were 12 patients (19 feet) in iliac crest group, including 9 males and 3 females with a median age M(Q1, Q3) of 11(11, 12) years and were followed-up for 36(6, 48) months. There were 9 patients (16 feet) in accessory navicular group, including 6 males and 3 females, with a median age M(Q1, Q3) of 11(11, 11) years and were followed-up for 12(6, 17) months. Radiographic evaluations were reviewed and compared between the two groups before surgical treatment and at final follow-up, included talo-1st metatarsal angle (T1MT), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA) in weight bearing anteroposterior view, and Meary angle, calcaneal Pitch angle, Kite angle, cuneiform articular angle (CAA) in weight bearing lateral view, and hindfoot alignment angle (HAA) in calcaneal long axial view. Functional scores included American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Maryland scores were recorded and compared before and after the operation. The complications were also recorded. Results: Total of 21 patients were successfully followed in this study. The radiographic measurements in the two groups, such as T1MT, TNCA, Meary angle, Pitch angle, Kite angle, CAA, HAA, were all significantly improved at the last follow-up when compared with those before the surgery (all P<0.05); and the AOFAS, VAS, Maryland scores in both groups were all improved after the surgery (all P<0.05). There was a significant difference in CAA alteration (∆CAA) after the operation between the two groups, the ∆CAA in iliac crest group and the accessory navicular group was 6.0°±2.6° and 4.3°±1.3°, respectively (P=0.017). There was no significant differences in the improvement of other radiographic measurements between the two groups (all P>0.05). All the patients had a successful bone union. Two patients had donor site pain in the iliac crest group and were treated conservatively. Conclusion: Compared with iliac crest bone graft, accessory navicular bone graft could achieve comparable outcomes in radiographic measurements and functional scores in the treatment of pediatric flexible flatfoot with accessory navicular pain.

[Advances in the role of autoimmune mechanisms in chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease whose pathogenesis mainly involves airway remodelling and alveolar destruction caused by inflammation, protease-antiprotease imbalance, oxidative stress, and imbalance between apoptosis and compensatory repair of lung tissue structure cells. In recent years, the role of the autoimmune response in COPD has attracted widespread attention, but there is still some controversy. This article reviewed the role of autoimmunity in COPD from different perspectives, starting with the relationship between autoimmunity and the pathogenesis of COPD.

[Analysis of effective connectivity in default mode network in male long-term smokers based on dynamic causal modeling].

Objective: To investigate the alterations in effective connection of default mode network (DMN) in long-term male smokers and its correlation with clinical characteristics of smoking. Methods: A total of 131 subjects through WeChat platform and underwent resting-state functional magnetic resonance (rs-fMRI) examinations were recruited, including 76 long-term smokers [long-term smoking group, male, aged 20 to 55 (32.1±6.3) years] and 55 non-smokers [healthy controls, male, aged 20 to 55(32.3±7.4) years] from January 2014 to December 2018. Long-term smokers were defined as those who smoked at least 10 cigarettes per day for more than 2 years, and met the Diagnostic and Statistical Manual of Mental Disorders-Four Edition (DSM-Ⅳ) criteria for substance dependence. Four major nodes of DMN, including left inferior parietal lobule (LIPL), right inferior parietal lobule (RIPL), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) were chosen as for the region of interest. The effective connectivity (EC) alterations of DMN between smoking group and healthy controls were compared using dynamic causal modeling (DCM). The correlation between EC with significant difference among the two groups and Nicotine Dependence Scale (FTND) score, pack-year score and smoking duration were evaluated. Results: Compared to the healthy controls, the EC of LIPL to PCC and PCC to mPFC were decreased in the smoking group (EC = -0.091, -0.174, respectively, Bayesian-PP>0.95), and the EC of RIPL to PCC was increased (EC = 0.136, Bayesian-PP>0.95). Besides, EC of LIPL to PCC showed negative correlation with pack-year scores(r=-0.282,P=0.017). No significant linear correlations were observed between EC with significant group difference and FTND score or smoking duration (r=-0.103、-0.089,all P>0.05). Conclusion: Long-term smokers showed multiple abnormalities in IPL-PCC-mPFC circuits, and associated with the pack-year scores.

[Retrospective analysis and a cross-sectional questionnaire survey of lung cancer concomitant with interstitial lung disease].

Objective: To describe the clinical characteristics and prognosis of lung cancer concomitant with interstitial lung disease (LC-ILD), and to understand the current status of knowledge of LC-ILD by physicians in the departments related to the treatment of the disease. Methods: We conducted a retrospective analysis of in-hospitalized pathology identified lung cancer (LC) patients who were admitted to our hospital between January 2014 and December 2018. After reviewing their chest CT imagings and pathological reports, 70 patients who were concomitant with interstitial lung disease (ILD) were enrolled in our study. On the other hand, a cross-sectional survey using an online questionnaire was conducted in LC-ILD management doctors who came from 29 provincial hospitals. The perceptions of demographic features, LC characteristics and management, ILD characteristics and management, and the prognosis of LC-ILD were investigated. Results: Among the 70 enrolled LC-ILD cases, there were 52 males, and the mean age was (64.3±7.63) years (ranged from 49 years to 84 years). There were 51 patients who were older than 59 years. The most common pathological pattern of LC was adenocarcinoma. Most of them were diagnosed with LC and ILD simultaneously, and they were usually treated with chemotherapy while unresectable. There were 11 patients (15.7%) with positive EGFR or ALK mutation. Forty-five patients (64.3%) died during the follow-up, and 33 were died from LC progression. There were no significant differences between the surgical group and non-surgical group on age, pathological patterns, EGFR or ALK mutation. However, LC-ILD patients in the surgical group were diagnosed with earlier TNM classification and with better prognosis. A total of 1 014 doctors answered the questionnaire completely. In the feedback, patients aged 60 years and older (785 doctors/77.4%), and male patients (720 doctors/71%) were the predominant LC-ILD patients. Adenocarcinoma (390 doctors/38.5%), adenocarcinoma or squamous-cell cancer (SCC) (182 doctors/17.9%), and SCC (151 doctors/14.9%) were considered as the common pathological patterns of LC-ILD patients. In most doctors' feedback, the EGFR or ALK mutation was not common for LC-ILD: low (646 doctors/63.7%) or hardly (306 doctors/30.5%) positive mutation. The diagnosis of ILD was earlier than LC (506 doctors/49.9%) or there was no identified precedence of LC and ILD diagnosis (208 doctors/20.5%). Most of the doctors (693 doctors/68.3%) agreed that the vital factor for surgery or not was the severity of ILD for LC-ILD patients. There were great divergences on the treatment protocol both for the advanced LC and ILD. The patients with LC-ILD were died mostly from LC progression and ILD exacerbation (542 doctors/53.5%), followed by ILD exacerbation (237 doctors/23.4%) or LC progression (226 doctors/22.3%). Conclusions: The elderly male patients were predisposed to LC-ILD, and adenocarcinoma was the common pathological pattern. The LC-ILD patients with non-advanced LC who were performed with surgery had better prognosis. However, it is recommended to consider whether to perform surgery in combination with the severity of the ILD.

[Analysis of liver cancer screening results and influencing factors of urban residents in Zhejiang Province from 2013 to 2018].

Objective: To analyze the results of liver cancer screening for urban residents in Zhejiang Province from 2013 to 2018 and explore the influencing factors of the detection rate. Methods: From September 2013 to August 2019, six urban communities in Hangzhou (Jianggan District and Gongshu District), Ningbo (Haishu District, Yinzhou District and Jiangbei District), and Quzhou (Kecheng District) were selected as study sites. All permanent residents aged 40-74 (with local household registration and living in the local area for more than 3 years) were selected as the research subjects by using cluster sampling method. Patients with confirmed cancers and other serious medical and surgical diseases were excluded. A total of 166 293 research subjects were included. Basic demographic characteristics and risk factors of subjects were obtained through questionnaire surveys. The cancer risk assessment system was used to evaluate the liver cancer risk of subjects. Clinical screening participation and screening results for subjects at high risk of liver cancer were obtained from participating hospitals. The high-risk rate of liver cancer, clinical screening rate, detection rate of positive lesions, and detection rate of suspected liver cancer were analyzed. Poisson regression was used to analyze the influencing factors of detection rate. Results: The age of 166 293 subjects was (56.01±8.40) years, of which 41.36% (68 777) were males. A total of 23 765 high-risk subjects for liver cancer were screened (the high-risk rate was 14.29%). Among them, a total of 12 375 subjects participated in clinical screening for liver cancer, with a screening rate of 52.07% (12 375/23 765). A total of 297 cases of positive lesions were detected and the detection rate was 2.40% (297/12 375). A total of 8 cases of suspected liver cancer were detected, with a detection rate of 0.06% (8/12 375). The results of multivariate Poisson regression model analysis showed that compared with men, people who never smoked, never ate pickled food, had low oil content, and had no history of hepatobiliary disease, female, people who were smoking or had smoked, sometimes ate pickled food, ate higher oil content, and had a history of hepatobiliary disease had a higher detection rate of positive lesions. The incidence rate ratio (IRR) (95%CI) values were 1.98 (1.45-2.70), 2.23 (1.61-3.09)/2.08 (1.31-3.28), 1.82 (1.22-2.70), 1.44 (1.08-1.91), and 1.45 (1.05-2.00), respectively. Compared with those aged from 40 to 49 years old and without HBsAg test, the IRR (95%CI) of suspected liver cancer in people aged 70 to 74 years old and HBsAg positive were 16.30 (1.32-200.74) and 6.43 (1.24-33.22), respectively. Conclusion: The urban cancer early diagnosis and early treatment project in Zhejiang Province has good compliance in clinical screening of liver cancer. Abdominal ultrasound examination and serum alpha-fetoprotein detection are helpful to detect liver cancer and its precancerous lesions in the high-risk population of liver cancer.

[Hepatic metastases after cervical cancer surgery: clinical analysis of 13 cases].

Objective: To investigate the clinical characteristics of patients with hepatic metastasis after cervical cancer operation, and analyze the risk factors and prognostic factors of hepatic metastasis. Methods: A total of 1 312 patients with stage Ⅰa2-Ⅱb2 cervical cancer received radical surgery from January 2013 to January 2016 in the First Affiliated Hospital of Zhengzhou University were collected, of which 13 cases (0.99%, 13/1 312) had hepatic metastasis after operation. A retrospective analysis was conducted on clinical features of patients with hepatic metastasis after cervical cancer operation. T-test, chi-square test, rank sum test and logistic regression were used to analyze the risk factors of hepatic metastasis after surgery of cervical cancer operation. Kaplan-Meier method was used for survival analysis. Log-rank test was used for screening of prognostic factors in patients with postoperative hepatic metastasis. Results: (1) Clinical features: there were 3 cases of simple hepatic metastasis without obvious clinical symptoms, 2 patients with perihepatic lymph node metastasis showed only low back pain, 8 patients with multiple extrahepatic metastases, and their clinical symptoms were related to the site of metastasis. Five cases out of 9 (5/9) with liver metastasis had abnormal tumor marker results. The abnormal kinds of tumor markers were mainly carcinoembryonic antigen (CEA), CA(125), CA(199), and CA(72-4). The interval time of hepatic metastasis after operation was 2-22 months. (2) Analysis of risk factors for hepatic metastasis: univariate analysis showed that lymph node metastasis, histological type, infiltration depth, and lymph-vascular space invasionwere associated with hepatic metastasis after cervical cancer surgery (P<0.05).Multivariate analysis showed that lymph node metastasis and small cell carcinoma were independent risk factors for postoperative hepatic metastasis (P<0.05). (3) Prognostic factors in patients with hepatic metastasis:among 13 patients with postoperative hepatic metastases from cervical cancer, 9 died during the follow-up period and 4 survived. The median total survival time after hepatic metastases was 7 months (range 3-32 months). Univariate analysis showed that multiple extrahepatic metastases and treatment after hepatic metastasis had significant effects on the prognosis of patients with hepatic metastasis after cervical cancer operation (P<0.05). Conclusions: The interval of hepatic metastasis after surgery for cervical cancer operation is within 2 years. Patients with lymph node metastasis and small cell carcinoma are more prone to postoperative hepatic metastasis. The prognosis of patients with extrahepatic multiple metastases is poor, and individualized treatment should be carried out after comprehensive analysis for patients with hepatic metastasis after cervical cancer operation.

The aberrant activation of Wnt pathway caused by ß-catenin mutation and its prognostic significance in NK/T-cell lymphoma.

The aberrant activation of the Wnt/ß-catenin signal has an important role in the progression of cancers. Herein, we investigated ß-catenin mutation and the activation of the Wnt pathway in association with the clinical-pathological characteristics, chemo-resistance and prognosis of NK/T-cell lymphoma (NKTCL). Real-time quantitative PCR, immunocytochemistry and immunohistochemistry SP methods detected the levels of ß-catenin, c-myc and cyclin D1 in human NKTCL cell lines (SNK-6 and YTS) and NKTCL tissues. Mutation analysis was detected in exon 3 of ß-catenin gene; and we analyzed cell viability after histone deacetylase inhibitor (HDACi) treatment. As a result, 19 (38%) of NK/T-cell lymphoma displayed nuclear ß-catenin and 16 (32%) contained mutations in exon 3; while no mutations were detected in lymphomas negative for ß-catenin nuclear staining (p<0.05). Most mutations affecting ß-catenin were adjacent to regulatory phosphorylation sites. ß-catenin, c-myc and cyclin D1 were significantly elevated in SNK-6 and YTS cell lines compared to normal NK/T cells (p<0.05). Furthermore, the high expression of ß-catenin, c-myc and cyclin D1 significantly correlated with the III/IV Ann Arbor stage. Additionally, the expression of ß-catenin in the SNK-6 cell line decreased significantly after treatment with HDACi, and Kaplan-Meier survival analysis revealed that the elevated expression of ß-catenin correlated with poor prognosis in NKTCL patients (23.66±2.77 months vs 31.65±1.78 months, p=0.023). In conclusion: mutations in exon 3 of ß-catenin and the activated Wnt pathway are common in NK/T-cell lymphoma that has nuclear ß-catenin, and it is closely correlated with the Ann Arbor stage and prognosis in NKTCL patients.

[PD-L1 expression is related with prognosis of small cell lung cancer].

Objective: To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC). Methods: The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed. Results: Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006). Conclusions: PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.

[Evaluation of clinical outcomes of allogeneic hematopoietic stem cell transplantation for relapsed/refractory peripheral T-cell lymphoma with chemoresistance].

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.

Relationship between Changes of Pericyte Number and Wound Age during Repair of Skeletal Muscle Contusion in Mice.

ABSTRACT: Objective To observe the change pattern of pericyte number at different time periods after mice skeletal muscle contusion and discuss its role in wound age estimation. Methods A mice gastrocnemius muscle contusion model was established. The form and number changes of pericytes at 1, 3, 5, 7, 9, 14, and 28 d post-injury were detected by multiple immunofluorescence staining. Results Compared with the slender shape of pericytes in normal skeletal muscles, pericytes in the contusion area had increased volume, rounder form and a round nuclei. Part of pericytes were found to express satellite cell markers paired-box transcription factor （Pax7） or myoblast determination 1 （MyoD1）. The changes of pericyte number in skeletal muscles after contusion were time-dependant, and showed unimodal distribution with the extension of wound age. In the central contusion area, the number of pericytes peaked at 5 d post-injury while in the peripheral contusion area, the number of pericytes peaked at 5 d and 7 d post-injury. Conclusion The number of pericytes in contusion area varies time-dependently after skeletal muscle contusion in mice and might be a reference index for muscle wound age estimation, and is involved in the repair and regeneration of skeletal muscle injury.

Relationship between the Degeneration and Regeneration of Neuromuscular Junction and Wound Age during the Repair of Mouse Skeletal Muscle Contusion.

ABSTRACT: Objective To investigate the morphological changes in the degeneration and regeneration of neuromuscular junctions （NMJ） during the repair of mouse skeletal muscle contusion and discuss the correlation between the degeneration and regeneration of NMJ and wound age. Methods A total of 50 healthy adult male mice were randomly divided into 10 groups, including 9 experimental groups and 1 control group. Immunofluorescent staining was applied, and neurofilament was marked with neurofilament protein-H （NF-H）, presynaptic membrane was marked with synaptophysin （Syn）, presynaptic membrane was marked with acetylcholine receptor （AChR）. Morphological changes of NMJ regeneration at different time points after mouse skeletal muscle contusion were detected. Results The neurofilament and presynaptic membrane of NMJ at the junction of contusion zones began to degrade after contusion, and completed degradation at about 3 d post-injury. Then they gradually regenerated, roughly completing the regeneration at about 21 d and basically reaching the control group level. The ratio of presynaptic membrane quantity to presynaptic membrane quantity showed a trend of decreasing then rising and finally reaching the control level. Conclusion During the repair of mouse skeletal muscle contusion, the morphological changes and wound age of the NMJ at the junction of contusion zones have a close correlation, which is expected to be one of the biological indicators for forensic skeletal muscle wound age estimation.

Relationship between Expression Changes of CB2R and Wound Age of Brain Contusion in Mice.

ABSTRACT: Objective To investigate the expression of cannabinoid type 2 receptor （CB2R） at different time points after brain contusion and its relationship with wound age of mice. Methods A mouse brain contusion model was established with PCI3000 Precision Cortical Impactor. Expression changes of CB2R around the injured area were detected with immunohistochemical staining, immunofluorescent staining and Western blotting at different time points. Results Immunohistochemical staining results showed that only a few cells in the cerebral cortex of the sham operated group had CB2R positive expression. The ratio of CB2R positive cells gradually increased after injury and reached the peak twice at 12 h and 7 d post-injury, followed by a decrease to the normal level 28 d post-injury. The results of Western blotting were consistent with the immunohistochemical staining results. Immunofluorescent staining demonstrated that the changes of the ratio of CB2R positive cells in neurons, CB2R positive cells in monocytes and CB2R positive cells in astrocytes to the total cell number showed a single peak pattern, which peaked at 12 h, 1 d and 7 d post-injury, respectively. Conclusion The expression of CB2R after brain contusion in neurons, monocytes and astrocytes in mice suggests that it is likely to be involved in the regulation of the biological functions of those cells. The changes in CB2R are time-dependent, which suggests its potential applicability as a biological indicator for wound age estimation of brain contusion in forensic practice.

The effectiveness of transport in a toy car for reducing preoperative anxiety in preschool children: a randomised controlled prospective trial.

BACKGROUND: This study was designed to determine whether transport of a paediatric inpatient in a children's ride-on toy car has an effect on perioperative levels of anxiety compared with transport on a hospital gurney with or without oral midazolam premedication. METHODS: In this prospective study, 108 children aged 2-5 yr with congenital heart disease and undergoing first surgical correction were randomly allocated to one of three groups: Group C (transport in a children's ride-on car), Group G (transport on a gurney without premedication), or Group M (transport on a gurney and received premedication of oral midazolam 0.5 mg kg-1). The modified Yale Preoperative Anxiety Scale-Short Form and parent-recorded anxiety VAS were applied to evaluate anxiety in the following time points: pre-anaesthesia visit (the day before surgery), upon getting in the ride-on car or on the gurney in the ward, upon arriving in the preoperative holding area, at the moment of leaving from the holding area to the operating room (OR) (coincided with separation from parents), at the time after entering the OR, and at the time just before anaesthesia induction. RESULTS: Children in Group C exhibited significantly lower levels of anxiety from the time they got into the ride-on car until the time they entered the OR, compared with the other two groups (P<0.001). The subjects in Group C had similarly low anxiety levels to those in the Group M at the time before induction (P=0.914). CONCLUSIONS: Transport in a ride-on toy car can relieve preoperative anxiety in preschool children undergoing surgery to a comparable degree as midazolam. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-17012791.

Pharmacokinetics of dexmedetomidine administered to patients with end-stage renal failure and secondary hyperparathyroidism undergoing general anaesthesia.

WHAT IS KNOWN AND OBJECTIVE: The primary objective of this study was to compare the pharmacokinetics of dexmedetomidine in patients with end-stage renal failure and secondary hyperparathyroidism with those in normal individuals. METHOD: Fifteen patients with end-stage renal failure and secondary hyperparathyroidism (Renal-failure Group) and 8 patients with normal renal and parathyroid gland function (Control Group) received intravenous 0.6 µg/kg dexmedetomidine for 10 minutes before anaesthesia induction. Arterial blood samples for plasma dexmedetomidine concentration analysis were drawn at regular intervals after the infusion was stopped. The pharmacokinetics were analysed using a nonlinear mixed-effect model with NONMEM software. The statistical significance of covariates was examined using the objective function (-2 log likelihood). In the forward inclusion and backward deletion, covariates (age, weight, sex, height, lean body mass [LBM], body surface area [BSA], body mass index [BMI], plasma albumin and grouping factor [renal failure or not]) were tested for significant effects on pharmacokinetic parameters. The validity of our population model was also evaluated using bootstrap simulations. RESULTS AND DISCUSSION: The dexmedetomidine concentration-time curves fitted best with the principles of a two-compartmental pharmacokinetic model. No covariate of systemic clearance further improved the model. The final pharmacokinetic parameter values were as follows: V1  = 60.6 L, V2  = 222 L, Cl1  = 0.825 L/min and Cl2  = 4.48 L/min. There was no influence of age, weight, sex, height, LBM, BSA, BMI, plasma albumin and grouping factor (renal failure or not) on pharmacokinetic parameters. Although the plasma albumin concentrations (35.46 ± 4.13 vs 44.10 ± 1.12 mmol/L, respectively, P < .05) and dosage of propofol were significantly lower in the Renal-failure Group than in the Control Group (81.68 ± 18.08 vs 63.07 ± 13.45 µg/kg/min, respectively, P < .05), there were no differences in the context-sensitive half-life and the revival time of anaesthesia between the 2 groups. WHAT IS NEW AND CONCLUSION: The pharmacokinetics of dexmedetomidine were best described by a two-compartment model in our study. The pharmacokinetic parameters of dexmedetomidine in patients with end-stage renal failure and hyperparathyroidism were similar to those in patients with normal renal function. Further studies of dexmedetomidine pharmacokinetics are recommended to optimize its clinical use.

Migration and invasion enhancer 1 (MIEN1) is overexpressed in breast cancer and is a potential new therapeutic molecular target.

Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein that is highly expressed in various types of cancer, and is correlated with the PI3K/AKT pathway. The aim of this study was to investigate the expression of MIEN1 and its clinical pathological significance in breast cancer. We used immunohistochemical staining to examine the expression of MIEN1 in 40 samples of human breast cancer tissue and 10 samples taken from regions adjacent to normal breast tissue. The rate of detection of MIEN1 protein was 67.5%, which was significantly higher than that in adjacent non-cancerous breast tissue (0%, P < 0.05). The expression of MIEN1 correlated with age, World Health Organization grade, and lymph node metastasis, but not with tumor size or family history of cancer. Kaplan-Meier survival analysis showed that patients with positive MIEN1 protein expression had a lower overall survival rate than patients who did not express MIEN1. Downregulation of MIEN1 suppressed the expression of matrix metallopeptidase 9 by downregulating the expression of protein kinase B (also known as AKT) in breast cancer cells. Our results indicate that MIEN1 overexpression may facilitate migration and invasion in breast cancer, and MIEN1 is a potential molecular target for cancer chemotherapy.

[Forensic Analysis of 6 Cases of Sudden Death due to Hyperthyroid Heart Disease].

OBJECTIVES: To analyse the cases of sudden death due to hyperthyroid heart disease, and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases. METHODS: Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine, China Medical University. The general information （gender and age）, clinical manifestations, medical history, anatomical and histopathological findings, biochemical parameters and cause of death were analysed retrospectively. RESULTS: Most of the 6 patients had definite history of hyperthyroidism, and they all showed certain degrees of symptoms of cardiovascular disease; had obvious incentive factors of death; histopathological examination of thyroid conformed to the performances of diffuse toxic goiter; with increase of cardiac weight, dilatation of cardiac chambers, myocardial hypertrophy and focal necrosis; postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease. CONCLUSIONS: The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy, histopathological examination, postmortem toxicology tests. The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary.