Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Humans ; Fentanyl/therapeutic use* ; Opioid-Related Disorders/drug therapy* ; Drug Overdose/prevention & control* ; Analgesics, Opioid/adverse effects* ; Vaccines/therapeutic use* ; Brain

BACKGROUND: Accurate serum total thyroxine (TT4) measurement is important for thyroid disorder diagnosis and management. We compared the performance of six automated immunoassays with that of isotope-diluted liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) as the reference method. We also evaluated the correlation of thyroid stimulating hormone (TSH) with TT4 measured by ID-LC-MS/MS and immunoassays. METHODS: Serum was collected from 156 patients between October 2015 and January 2016. TT4 was measured by immunoassays from Abbott (Architect), Siemens (ADVIA Centaur XP), Roche (E601), Beckman-Coulter (Dxi800), Autobio (Autolumo A2000), and Mindray (CL-1000i), and by ID-LC-MS/MS. Results were analyzed using Passing-Bablok regression and Bland-Altman plots. Minimum requirements based on biological variation were as follows: a mean bias of ≤4.5% and total imprecision (CV) of ≤3.7%. RESULTS: All immunoassays showed a correlation >0.945 with ID-LC-MS/MS; however, the slope of the Passing-Bablok regression line varied from 0.886 (Mindray) to 1.23 (Siemens) and the intercept from −12.8 (Siemens) to 4.61 (Mindray). Only Autobio, Beckman-Coulter, and Roche included the value of one in the 95% confidence interval for slope. The mean bias ranged from −10.8% (Abbott) to 9.0% (Siemens), with the lowest value noted for Roche (3.5%) and the highest for Abbott (−10.8%). Only Abbott and Roche showed within-run and total CV ≤3.7%. CONCLUSIONS: Though all immunoassays correlated strongly with ID-LC-MS/MS, most did not meet the minimum clinical requirement. Laboratories and immunoassay manufacturers must be aware of these limitations.
Bias (Epidemiology) ; Diagnosis ; Humans ; Immunoassay ; Mass Spectrometry ; Methods ; Thyroid Gland ; Thyrotropin ; Thyroxine

Objective The aim of this study was to evaluate theβ-cell mass ( BCM) in patients with type 2 diabetes mellitus( T2D) by PET/CT using [ 18 F]-FP-(+)-DTBZ, which is a vesicular monoamine transporter type 2 molecular probe. The feasibility of pancreatic head, body and tail as the target area was investigated for evaluation of the BCM in T2D. Methods 15 subjects ( 8 with T2D, and 7 as control) were involved in this study with 20 min static PET imaging at 40 min post injection of [ 18 F]-FP-(+)-DTBZ. The volume of interest ( VOIs) of pancreatic head, body and tail were drawn and quantitatively assessed. Spleens were collected as reference tissue for SUVR calculation. Results SUVR in the pancreatic head ( SUVR=1.72 ± 0.47) and pancreatic body, tail ( SUVR=1.85 ± 0.41) in T2D group was no significant difference, and no significant difference was observed in the pancreatic head (SUVR=2.54±0.57) and pancreatic body, tail(SUVR=2.73±0.41) in control group as well. In T2D group, a significant decreased SUVR was found in pancreatic head (P=0.0088) and pancreatic body and tail (P=0.0012) compared with controls. Conclusion The VMAT2 molecular probe [ 18 F]-FP-(+)-DTBZ can be used to evaluate BCM in patients with T2D.

Objective To investigate the effects of club mode of health education on social support of breast cancer patients and their spouses.Methods A total of 100 breast cancer patients who underwent modified radical mastectomy and their spouses in Suzhou Municipal Hospital from May 2012 to March 2013 were randomly divided into the intervention group and the control group with 50 cases respectively. Patients and spouses in the intervention group were involved in the club, while in the control group patients and spouses received routine nursing care. Perceived social support scale (PSSS) and social support ratings scale (SSRS) were used in the questionnaires for patients before the intervention and at the 1st month, 3rd month, 6th month after the intervention.Results In the intervention group, the score of the support on the patients out of family was (29.80±5.77) at the 1st month after the intervention; the total score of perceived social support was (57.22±5.26) at the 3rd month after the intervention; the score of support from family was (26.59±2.51) at the 6th month after the intervention. All of those scores were significant higher than those in the control group (F=6.391, 0.304, 7.435;P<0.05). At the 3rd month after the intervention, the score of the social support on the spouses were (45.02±6.40) in the intervention group and (39.17±7.77) in the control group. The difference between the two groups was statistically significant (F=1.250,P<0.05).Conclusions The club mode of health education can effectively improve the social support status for breast cancer patients and their spouses.

Objective To investigate the value of electronic bronchoscopy in the diagnosis of children respiratory diseases. Methods The electronic bronchoscopy results in 400 children with respiratory disease were retrospectively analyzed. Results In 400 children, there were 246 cases with simple endobronchial inflammation, 67 cases with bronchial malacia, 38 cases with bronchial stenosis, 23 cases with bronchial foreign , 4 cases with tracheal bronchus, 4 cases with epiglottic cyst, 3 cases with bronchiectasis, 3 cases with endobronchial granulation, 3 cases with laryngomalacia, 2 cases with vascular ring compression of the trachea, 2 cases with laryngeal web, 1 case with subglottic cyst, 1 case with subglottic neoplasm, 1 case with tracheoesophageal fistula, 1 case with bronchial atresia (left) and 1 case with trachea cyst. All the children had no serious complications. Conclusions Electronic bronchoscopy can effectively improve the level of diagnosis and treatment of children' s respiratory system disease, and it is worth of clinical promotion.

Objective To compare the clinical effects of palpation, ultrasound and electromyography (EMG) guided injection of botuli-num toxin type A (BTX-A) on spastic equinovarus in stroke patients. Methods Stroke patients with equinovarus were randomly assigned to palpation-guided group (n=19), ultrasound-guided group (n=21) and EMG-guided group (n=19). All of the patients received injection of BTX-A 300 U in gastrocnemius, soleus and tibialis posterior, guided in their own ways. They were measured with modified Ashworth Scale (MAS), Physician Rating Scale (PRS), speed of gait, passive range of motion (PROM) of ankle dorsiflexion and eversion before and 2 weeks, 4 weeks, 8 weeks, and 12 weeks after injection. Results Compared with the baseline, all the indexes significantly improved after in-jection in all the groups (P<0.05). Compared with the EMG-guided group, the ultrasound-guided group improved significantly MAS at 4 weeks, PROM of ankle eversion at 4 and 12 weeks (P=0.046, P=0.008, P=0.038). Compared with the palpation-guided group, the ultra-sound-guided group improved significantly in MAS (P=0.015), PRS (P=0.01), PROM of ankle dorsiflexion and eversion (P=0.003, P=0.011) at 4 weeks, in MAS (P=0.002) and PROM of ankle dorsiflexion (P=0.022) at 8 weeks, in MAS (P=0.011) and PROM of ankle ever-sion (P=0.018) at 12 weeks. Compared with the palpation-guided group, the EMG-guided group improved significantly in PRS at 4weeks, PROM of ankle dorsiflexion at 4 and 8 weeks (P=0.048, P=0.08, P=0.026). There was no significantly difference in the variations with the time among 3 groups. Conclusion The correction of equinovarus in stroke patients can be obtained by BTX-A injection with any type of guidance technique. Ultrasound-guided technique is considered a valid alternative, which has a slight advantage over EMG-guided tech-nique. Both the EMG-and ultrasound-guided techniques obtained superior results to palpation-guided technique.

Objective To investigate the relationship between the mechanism of gynecomastia and serum hormone levels ,as well as liver function in male patients with liver cirrhosis .Methods Forty‐six male patients with liver cirrhosis and gynecomastia were collected as gynecomastia group from March 2013 to March 2014 ,and at the same period seventy male patients with liver cirrhosis but without gynecomastia were studied as non‐gynecomastia group . The condition of mammogenesis and maximum of breast thickness were measured by bilateral breast ultrasound .Hormones including luteinizing hormone (LH) ,follicle‐stimulating hormone (FSH) , prolactin (PRL) ,estradiol (E2) ,progesterone (PRGE) ,and testosterone (T);liver function including alanine aminotransferase (ALT) ,aspartate aminotransferase (AST) ,total bilirubin (TBil) and serum albumin (Alb);blood coagulation function including prothrombin time (PT) ,platelet count (PLT) were examined and the Child‐Pugh scores were calculated .t‐test was performed for results comparison between gynecomastia group and non‐gynecomastia groups .Chi‐square test was used to compare the difference in drinking rate between two groups . The patients of gynecomastia group and non‐gynecomastia group were further divided into Child‐Pugh Grade A ,B and C subgroups according to Child‐Pugh scores and the patients of gynecomastia group were divided into subgroups according etiology such as posthepatitic cirrhosis ,alcoholic liver cirrhosis and posthepatitic cirrhosis combined with alcoholc cirrhosis .Single factor analysis of variance was applied to compare the laboratory findings between subgroups ,and least‐significant difference mothod was used to further compared the differences between two subgroups .Results Among forty‐six male patients with liver cirrhosis and gynecomastia ,the mean thickness of breast was (7 .56 ± 2 .84) mm .All the differences of TBil ,Alb ,PT and Child‐Pugh score of Child‐Pugh grade patient were statistically significant between gynecomastia group and no gynecomastia group ((96 .72 ± 75 .86)μmol /L vs (60 .57 ± 54 .00)μmol /L ,(29 .12 ± 4 .90) g/L vs (33 .86 ± 6 .86) g/L ,(19 .06 ± 4 .76) s vs (15 .54 ± 2 .57) s ,11 .54 ± 0 .91 vs 10 .33 ± 0 .57 ,respectively ,t=2 .79 ,-4 .33 ,4 .58 ,2 .22 ,all P<0 .05) . The alcoholic drinking rate of gynecomastia group (74% (34/46) vs 53% (37/70)) increased ,and the difference was statistically significant compared with that of non‐gynecomastia group (χ2 =5 .183 , P<0 .05) .There was no statistically significant difference in E2 levels between gynecomastia group and non‐gynecomastia group (P>0 .05) .PRL and E2/T ratio ((404 .49 ± 297 .26) mU/L and 68 .74 ± 46 .37) were higher than those of non‐gynecomastia group ((279 .77 ± 111 .57) mU/L and 13 .60 ± 11 .55) ,and T was lower than that of non‐gynecomastia group ((7 .15 ± 5 .74) nmol/L vs (15 .46 ± 8 .53) nmol/L) ,and the differences were statistically significant (t=2 .72 ,7 .90、-6 .27;all P<0 .05) .Among patients with gynecomastia ,breast of patients with alcoholic liver cirrhosis was significantly thicker than that of patients with posthepatitic liver cirrhosis ((9 .25 ± 3 .59) mm vs (6 .67 ± 2 .48) mm) ,while the level of PRGE was lower than that of patients with posthepatitic liver cirrhosis ((0 .61 ± 0 .51 ) nmol/L vs (1 .49 ± 1 .47 ) nmol/L ) , and the differences were statistically significant (F= 3 .634 and 2 .674 ,both P< 0 .05) .Along with the severity of liver injury ,E2 level of gynecomastia group gradually increased ,however there was non‐statistically significant difference compared with non‐gynecomastia group (P>0 .05) .T level of gynecomastia group gradually decreased ,and those of Child‐Pugh B ,C subgroup ((8 .20 ± 7 .58) nmol/L and (4 .18 ± 3 .76) nmol/L) were siginificantly lower than that of Child‐Pugh A subgroup of non‐gynecomastia group ((17 .64 ± 9 .04) nmol/L ,F=9 .37 ,P<0 .05) .The E2/T levels of gynecomastic group gradually increased .There was significant difference in E2/T level between Child‐Pugh C subgroup of gynecomastia group (105 .49 ± 94 .42) and Child‐Pugh A grade subgroup of non‐gynecomastia group (11 .38 ± 9 .60 ,F=12 .57 ,P<0 .05) .Conclusions There are different degrees of sex hormone disorder in the serum of male patients with liver cirrhosis and gynecomastia which is more significant in PRL ,T and E2/T .T and E2/T level are correlated with the degree of liver functional impairment .Gynecomastia in alcoholic liver cirrhosis is more severe than that of posthepatitic liver cirrhosis .

Objective To evaluate the role of expression of phosphodiesterase 4B (PDE4B) in the spinal cord in inflammatory responses in a rat model of neuropathic pain and the relationship with extracellular signal-regulated kinase (ERK).Methods Sixty healthy male Sprague-Dawley rats,weighing 180-220 g,in which intrathecal catheters were implanted at L5,6 interspace,were used.The location of catheters was confirmed 6 days later.The rats were randomly divided into 5 groups (n =12 each):sham operation group (group Sham),normal saline (NS) group,vehicle group (group Ⅴ),mismatch siRNA group (group siR-M),and PDE4B-siRNA group (group siR-B).Neuropathic pain was induced by ligation of L5 spinal nerve (SNL).In Sham group,the L5 spinal nerve was only exposed,but not ligated.Immediately after ligation and on 1,3,5,and 7 days after ligation,10 μl NS,10 μl NS,LipofectaminTM RNAiMAX,PDE4B-siRNA (2 μg/10 μl) encapsulated in mismatch siRNA and PDE4B-siRNA (2 μg/10 μl) encapsulated in LipofectaminTM RNAiMAX were injected intrathecally in Sham,NS,V,siR-M,and siR-B groups,respectively.The mechanical pain threshold was measured at 1 day before and 2,4,6 and 8 days after operation.After behavioral testing on 8th day after operation,the rats were sacrificed and the lumbar segment of the spinal cord was removed for determination of PDE4B protein,ERK and phosphor-ERK (p-ERK)expression,and TNF-α,IL-1β and IL-6 levels.Results Compared with Sham group,the mechanical pain threshold was significantly decreased at 2,4,6 and 8 days after operation in NS,V,siR-M and siR-B groups (P ＜0.05),and no significant change was found in the mechanical pain threshold at 2,4,6 and 8 days after operation (P ＞ 0.05) and the expression of p-ERK and PDE4B protein,and levels of TNF-α,IL-1β and IL-6 were increased at 2,4,6 and 8 days after operation in V and siR-M groups (P ＜ 0.05).Compared with NS group,the mechanical pain threshold was significantly increased,and the expression of p-ERK and PDE4B protein and levels of TNF-α,IL-1β and IL-6 were decreased at 2,4,6 and 8 days after operation (P ＜ 0.05),and no significant change was found in the parameters mentioned above in V and siR-M groups (P ＞ 0.05).Conclusion Up-regulation of the expression of PDE4B protein in the spinal cord is involved in the development of neuropathic pain in rats,which may be related to promoted phosphorylation of ERK in the spinal cord and enhanced inflammatory responses.

ObjectiveTo explore the psychological training methods on improving the mental adaptation and performance of recruits.MethodsAccording to army's squad establishment,372 recruits were randomly extracted and divided into intervention group (182) and control group (190).A series of special group psychological trainings,such as Warm barracks,Friendly Care,Self-awareness,Interpersonal communication,etc,was applied to the recruits of the intervention group through the squad leaders given psychological training.The effect was assessed with Psychosocial Stress Survey For Groups (PSSG),General Maladjustment Scale (GM),Social Support Rating Scale (SSRS),General Self-Efficacy Scale (GSES),Wallace Slef-Concept Scale (WSCS) and Examined Performance.ResultsThe scores of negative emotion was [(3.89±2.01) score vs (2.56±1.65) score ],negative copy was [(3.96±2.52) score vs (2.97±1.78)score],total stress was [(46.36±21.74)score vs (33.71±17.56) score],maladjustment was [(11.26±5.04)score vs (9.10±4.53)score] in the intervention group,which was significantly reduced than those in the control group(P＜0.01).But the scores of positive emotion was [(3.70±1.62) score vs (4.16±1.84) score],positive copy was [(5.21±1.94) score vs (6.93±2.17) score ],subjective support was [(21.37±3.59)score vs (22.56±3.53)score] and support utilization was [(7.03±2.16) score vs (8.92±2.44) score],self-concept was [(74.33±15.72) score vs (80.65±13.98) score],self-efficacy was [(2.44±0.56) score vs (2.91.±0.52) score ] and the examination performance was [(pull-up:(5.12±3.77) times vs (12.09±4.52) times; sit-up:(30.82±9.54) times/3 min vs (70.20±16.83) times/3min; push-up:(21.32±9.73)times/2 min vs (61.75±17.62)times/2 min; Running 3000 meters:(14.17±1.14) s vs (12.82±0.32) s; standing grade throw:(26.68±4.62) mvs (35.38±8.44) m ],which was significantly improved (P＜0.01 or P＜0.05).ConclusionsComprehensive group psychological training implemented by Squad leader could effectively improve the ability of adaptation of recruits and promote the performance.