The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*

【Objective】 To investigate the clinical characteristics and molecular genetic mechanism of 46,XY complete gonadal dysplasia (46,XY CGD) caused by a new mutation of NR5A1 gene. 【Methods】 The clinical data of a female patient with 46 XY karyotype were retrospectively analyzed, and the whole exon group and mitochondrial group genes were detected. 【Results】 The clitoris was hypertrophic. The patient had both urethral orifice and vaginal orifice, and there was no common passage between them. Ultrasonography showed an unclear primordial uterus and bilateral ovaries. The gonad biopsy showed poorly developed testicular tissue. Karyotype was 46,XY. The detection of whole exon group and mitochondrial group genes indicated a new heterozygous missense mutation in NR5A1 gene on chromosome 9, and the variation information was c.205C>T:p. Arg69Cys. The mother did not carry the gene mutation. 【Conclusion】 The clinical manifestations of 46,XY CGD are diverse. NR5A1 gene mutation is one of the important causes, which provides a basis for the clinical diagnosis and pathogenesis of the disease.

【Objective】 To explore the efficacy of Mathieu combined with tongue-shaped flap covering in children with distal hypospadias and micropenis head deformity. 【Methods】 The clinical data of 72 patients with distal hypospadias complicated with micropenis treated during Jan.2018 and Jun.2021 were retrospectively analyzed, including 35 patients who underwent modified Mathieu combined with tongue-shaped flap and external urethral orificium (study group), and 37 patients who underwent traditional Mathieu (control group). Urethral stricture, urethral fistula, urethral diverticulum and penile head cleft were compared between the two groups. 【Results】 Urinary fistula occurred in 2 cases (5.27%) and 9 cases (24.32%) in the study group and control group, respectively, the incidence being much lower in the study group (P=0.028). Urethral stricture occurred in 1 case (2.86%) and 1 case (2.70%) in the study group and control group, respectively; penile head dehiscence in 1 case (2.86%) and 3 cases (8.11%); urethral diverticulum in 0 case (0%) and 2 cases (5.41%). There were no significant differences between the two groups in the incidence of urethral stricture, urethral dehiscence and urethral diverticulum (P>0.05). 【Conclusion】 Mathieu combined with tongue-shaped flap covering to treat children with distal hypospadias with micropenis head deformity can reduce the incidence of postoperative complications, achieve high surgical satisfaction and appearance satisfaction in the first phase, reduce harm caused by surgery, and promote patients’ psychological health.

Objective:To investigate the advantages and disadvantages and clinical effects of integrated acetabular quadrilateral surface buttress plate in the treatment of acetabular both column fractures.Methods:From September 2017 to March 2019, 14 patients with acetabular both column fractures were treated with integrated quadrilateral acetabular buttress plate and were followed up. The clinical data were retrospectively analyzed. There were 10 males and 4 females with an average age of 53.2 years (range, 26-75 years). Fracture classification were both column fractures according to the Letournel-Judet classification system, including 11 cases of combined posterior wall without posterior dislocation. The time from injury to operation was 8-19 days, with an average of 10.3 days. All operations were performed with a supra-ilioinguinal approach. After satisfactory reduction, the integrated acetabular quadrilateral surface buttress plate was used to fix the anterior and posterior column and quadrilateral fractures at the same time. After operation, Matta criteria was used to evaluate the quality of fracture reduction on postoperative images, and modified Merle d'Aubigné-Postel score to evaluate hip joint function.Results:The average operation time was 180 min (range, 120-320 min), and the intraoperative average blood loss was 980 ml (range, 700-1 600 ml). Operations were performed successfully with none intraoperative reshaping conducted, and the plate could fit into the bone surface well. All 14 patients were followed up with an average of 15.6 months (range, 9-20 months). During the follow-up, all fractures healed with an average of 3 months (range, 2.5-5 months). The reduction quality evaluated by the Matta criteria were 7 anatomical, 5 satisfactory, and 2 unsatisfactory, with an excellent and good rate of 85.7% (12/14). The hip joint function at the last follow-up was in accordance with the modified Merle d'Aubigné-Postel score was 12-18 points, with an average of 16.9 points, of which 8 excellent, 4 good, and 2 fair. The excellent and good function rate was 85.7% (12/14). During the operation, 1 patient had a rupture of about 1 cm of the peritoneum during the separation of the spermatic cord, which was immediately sutured and repaired. One patient had obturator nerve paralysis after the operation, without special treatment, and the paralysis symptoms were relieved during the 6th-month follow-up. There were no other operation-related complications.Conclusion:For both-column fractures characterized by central dislocation of the femoral head, the integrated acetabular quadrilateral buttress plate can simultaneously fix the anterior and posterior columns and quadrilateral surface at the same time. Satisfactory reduction and functional outcomes could be achieved by the novel plates.

Objective:To investigate the relationship of triglyceride (TG), fasting blood glucose (FPG) and triglyceride glucose product index (TyG) with the incidence of hypertension, and provide basic data for the prevention and treatment of hypertension in the population.Methods:A total of 23 581 individuals who met the research criteria in Jinchang cohort were selected as the research subjects, the Cox proportional hazard model was used to analyze the relationship of TG, FPG, and TyG with the risk of hypertension. A stratified analysis was conducted by sex.Results:After adjusting for confounding factors, compared with the normal TG group, the HR(95% CI) of the elevated TG margin group and the elevated group were 1.16 (1.01-1.34) and 1.49 (1.30-1.70), respectively in the total population. Among men, they were 1.13 (1.01-1.27) and 1.17 (1.06-1.30), and among women, they were 1.05 (0.88-1.26) and 1.06 (0.88-1.28). Compared with the normal FPG group, the HR (95% CI) of the FPG-impaired group were 1.29 (1.13-1.48) in the total population, 1.26 (1.08-1.48) in men and 1.59 (1.14-2.21) in women. Taking the lowest quartile array as a reference, the HR (95% CI) of the highest quartile array of TyG was 1.73 (1.45-2.07) in the total population, 1.32 (1.14-1.53) in men and 1.87 (1.37-2.54) in women. TG, FPG had a nonlinear dose-response relationship with the risk of hypertension, while TyG had a linear correlation with the risk of hypertension. Conclusions:Higher TG, FPG, and TyG levels are independent risk factors for the incidence of hypertension. People with higher TG, FPG and TyG are at high risk for hypertension, to which close attention should be paid in the prevention and treatment of hypertension.

Objective:To share related knowledge and experiences with countries along the line, literature regarding current cohort studies was summarized. Distribution, establishment and development of cohort studies among large prospective general population were analyzed in 17 countries of Western Asia and the 16 countries of Central and Eastern Europe.Methods:Literature review was conducted to collect basic information on cohort studies, with descriptive study used to analyze the characteristics of these cohort studies.Results:There were 562 cohort studies with sample size as more than 1 000 stated in Western Asia and Central and Eastern Europe, including 468 (83.27 %) carried out in the nation itself and 94 (16.73 %) with international multicentered collaboration. According to the nature of cohort studies, 347 (61.74 %) were etiologically based. As for the contents involved, 310 (55.16 %) of them targeted on chronic/non-communicable diseases, 125 (22.24 %) concentrated on maternal and child health. Among those on chronic/non-communicable diseases, 51 (16.45 %) were on cancers and 83 (26.77 %) on cardiovascular disease studies. There appeared 10 large prospective cohort studies targeting on general population, mainly ongoing in Iran and European countries, with a duration of 8-29 years, including 4 of them with sample size as more than 50 000. In terms of the contents, epidemiological investigation, physical examination and biological samples collection took the major parts. Few papers were published in 9 out of the 10 cohort studies at the early stage of those projects but the number of papers increased annually and stabilized to certain extent. Conclusions:The regional distribution of cohort studies carried out in countries from the Western Asia and Central and Eastern European areas appeared unbalanced. Contents of these designs would mainly involve etiological studies, with focus on non-communicable diseases as cancer, cardiovascular disease, diabetes, respiratory diseases, mental and psychological diseases, and maternal and infant health etc.. However, only few large prospective cohort studies would base on general population.

Objective To evaluate the efficacy and safety of 3D printing patient-specific external guide template in assisting minimally invasive screwing for treatment of pelvic and acetabular fractures.Methods The clinical and follow-up data of 39 pelvic or acetabular fractures were retrospectively analyzed which had been treated from June 2016 to February 2018 at Department of Orthopaedics,Wuhan Union Hospital.The patients were divided into a template group and a freehand group.In the template group,there were 14 men and 7 women with an age of 46.3 ± 18.2 years and 17 pelvic fractures and 4 acetabular fractures;in the freehand group,there were 12 men and 6 women with an age of 43.8 ± 12.2 years and 14 pelvic fractures and 4 acetabular fractures.The 2 groups were compared in terms of operation time,fluoroscopic frequency,guide wire adjustments,fracture reduction,screw penetration rate,function evaluation and adverse events.Results All the 39 patients were followed up for 9 to 13 months (average,11.6 months).A total of 42 screws were placed in the template group and 35 screws in the freehand group.The values of operation time (43.8 ± 22.2 min),fluoroscopic frequency (29.6 ± 10.7 times) and guide wire adjustments (1.8 ± 1.2 times) in the external guide template group were all significantly lower than those in the freehand group (73.8 ±22.6 min,54.6 ± 16.5 times and 9.8 ±2.8 times,respectively) (P ＜0.05).There were no significant differences between the 2 groups in screw penetration rate,rate of satisfactory reduction,Majeed scores for pelvic function or modified Merle d'Aubigné scores at the last follow-ups (P ＞ 0.05).One case in the freehand group experienced numbness after operation on unilateral dorsi pedis which disappeared at 3-month follow-up.Conclusion The 3D printing patient-specific external guide template can reduce fluoroscopic frequency,save operation time and improve accuracy of screw insertion,providing a new means for minimally invasive treatment of pelvis and acetabular fractures.

Objective To investigate the relationship between changes in the liver computed tomography (CT) images and the postmortem interval (PMI) of rabbits 129 h after their death due to hemorrhagic shock. Methods CT scanning was used to investigate the hemorrhagic shock death model in 23 rabbits to identify the postmortem cerebral changes from 0 h to 129 h after death. Results The liver or lumbar area in the liver window showed the following characteristic changes: from unchanged, to rapid shrinkage, to slow shrinkage; the mean CT values of the liver initially increased and subsequently decreased. The regression equations for the relationship between the two indices and PMI were established by surgery, and they all had statistical significance (P ＜ 0. 01). Conclusion CT scanning can accurately show changes in the rabbit liver after death. The mean CT value of the liver tissue is more sensitive for inferring early PMI. Furthermore, the liver area/lumbar area ratio parameters are more sensitive for inferring mid-late PMI.