The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

Objective:To explore feasible surgical options for management of persistent Müllerian duct syndrome (PMDS) in children.Methods:A retrospective case summary was made.The clinical data of 8 patients who were diagnosed with PMDS and treated at Shanxi Children′s Hospital from September 2011 to November 2020 were retrospectively reviewed.Of the 8 PMDS patients, 6 were sporadic cases, 2 were twins (monochorionic), with an age range from 1 year to 12 years.All cases had normal male external genital organs and a chromosomal karyotype of 46, XY.During the operation, the surgical plan was selected according to clinical classification, vas structure and the development of the initial uterus.After the operation, the Müllerian structure in the abdominal cavity and the testicular development of the children were followed up through color ultrasound at the outpatient department.Results:Four patients had oblique inguinal hernia, 3 had bilateral cryptorchidism, and 1 had transverse testicular ectopia.Müllerian inhibitory hormone (MIH) levels were significantly decreased in 5 cases and normal in 1 case.The other 2 cases were not tested for MIH.All bilateral gonadal biopsies were testicular tissue, but undifferentiated gonadal tissue was detected in 3 cases.Four cases underwent radical surgery after gonadal biopsy.Among these 4 children, 3 received one-stage radical operation, and 1 received repair of oblique hernia before the radical surgery.Three patients had a well-defined vas structure and underwent hysterectomy and bilateral orchidopexy; three patients had a vague vas structure and received orchidopexy with the uterus preserved; one case underwent hysterectomy, orchidopexy on one side and orchiectomy on the other side; one case had bilateral orchidectomy in Fowler-Stephens stage.All the 8 children were followed up for 2 to 12 years.Ultrasound showed that the descending testis was well developed, with no cryptorchidism retraction or hernia recurrence.No tumor was observed in the preserved uterus in the abdominal cavity.Conclusions:The plan for PMDS management in children should be determined based on its clinical classification.Gonadal biopsy is essential, and whether to remove the Müllerian structure depends on the vas structure and the development of the uterus.

Objective:To investigate the efficacy and safety of transurethral incision for the treatment of ureterocele in infants.Methods:A retrospective analysis of 28 cases of ureterocele admitted from March 2012 to May 2023 were reviewed, all of which were less than 1 year old, 16 male and 12 female, with an average age of(5.7±3.5)months. The ureterocele was located on the left side in 8 cases, on the right side in 15 cases, and bilaterally in 5 cases. There were 12 cases of single system ureterocele, of which 7 cases were unilateral and 5 cases were bilateral. Duplex system ureterocele was observed in 16 cases, all of which were unilateral. Clinical manifestations: urinary tract infection in 13 cases, 11 cases of ureterocele or hydronephrosis and ureteral dilation were found during antenatal examination, and 4 cases of ureterocele were found after birth. Urological ultrasound, intravenous pyelography(IVP) and voiding cystourethrography(VCUG) were performed in all children, and 17 cases underwent magnetic resonance urolography (MRU), and confirm the diagnosis of ureterocele preoperatively. All of the cases were performed the transurethral incision.The ureterocele was punctured and incised 1-2 mm at the base of the bulge, and 2-4 points were punctured according to the bulge atrophy. Bilateral ureteroceles were punctured and incised simultaneously. Postoperative urine routine test, urinary tract color ultrasound and VCUG were performed to determine if there is urinary tract infection, hydronephrosis, ureteral dilation and bulging, and whether a second surgery is needed.Results:All operations were conducted successfully. The intraoperative bleeding was less than 3 ml and no intraoperative complications. The operative time was (28.4±10.3) min. The median postoperative follow-up was 34 (32, 36) months. Six cases underwent postoperative VCUG examination. Eleven children were recovered well with single systemic ureterocele. One child developed grade Ⅳ vesicoureteral reflux(VUR)and combined with bladder diverticulum, and ureterocele underwent open diverticulotomy and ureteral reimplantation six months after surgery. Nine children were recovered well with duplex systemic ureterocele. Six cases of children developed infection, of which 2 cases had an infection once within one month after TUI, and the other four cases still had intermittent infections after six months and VCUG was performed, and one case showed grade Ⅲ VUR of the lower ureter, which was observed conservatively, while the other three cases had enlarged cysts but no VUR, and upper heminephrectomy was performed, and the patients recovered well after surgery. Except for these 6 exceptions, in another case, after ten years of follow-up, the ureterocele became larger but no VUR, and the results were good after a second transurethral incision. There was no significant difference in the postoperative infections, new VUR cases, and secondary surgeries between the two groups.Conclusions:Transurethral incision has good surgical effect on children with single system ureterocele and duplex system ureterocele, and has advantages of easy operation, less trauma, safety and effectiveness, and few complications. It deserves to be recommended as the treatment of choice, especially for infants and young children.

Objective:To explore feasible surgical options for management of persistent Müllerian duct syndrome (PMDS) in children.Methods:A retrospective case summary was made.The clinical data of 8 patients who were diagnosed with PMDS and treated at Shanxi Children′s Hospital from September 2011 to November 2020 were retrospectively reviewed.Of the 8 PMDS patients, 6 were sporadic cases, 2 were twins (monochorionic), with an age range from 1 year to 12 years.All cases had normal male external genital organs and a chromosomal karyotype of 46, XY.During the operation, the surgical plan was selected according to clinical classification, vas structure and the development of the initial uterus.After the operation, the Müllerian structure in the abdominal cavity and the testicular development of the children were followed up through color ultrasound at the outpatient department.Results:Four patients had oblique inguinal hernia, 3 had bilateral cryptorchidism, and 1 had transverse testicular ectopia.Müllerian inhibitory hormone (MIH) levels were significantly decreased in 5 cases and normal in 1 case.The other 2 cases were not tested for MIH.All bilateral gonadal biopsies were testicular tissue, but undifferentiated gonadal tissue was detected in 3 cases.Four cases underwent radical surgery after gonadal biopsy.Among these 4 children, 3 received one-stage radical operation, and 1 received repair of oblique hernia before the radical surgery.Three patients had a well-defined vas structure and underwent hysterectomy and bilateral orchidopexy; three patients had a vague vas structure and received orchidopexy with the uterus preserved; one case underwent hysterectomy, orchidopexy on one side and orchiectomy on the other side; one case had bilateral orchidectomy in Fowler-Stephens stage.All the 8 children were followed up for 2 to 12 years.Ultrasound showed that the descending testis was well developed, with no cryptorchidism retraction or hernia recurrence.No tumor was observed in the preserved uterus in the abdominal cavity.Conclusions:The plan for PMDS management in children should be determined based on its clinical classification.Gonadal biopsy is essential, and whether to remove the Müllerian structure depends on the vas structure and the development of the uterus.

Objective:To investigate the efficacy and safety of transurethral incision for the treatment of ureterocele in infants.Methods:A retrospective analysis of 28 cases of ureterocele admitted from March 2012 to May 2023 were reviewed, all of which were less than 1 year old, 16 male and 12 female, with an average age of(5.7±3.5)months. The ureterocele was located on the left side in 8 cases, on the right side in 15 cases, and bilaterally in 5 cases. There were 12 cases of single system ureterocele, of which 7 cases were unilateral and 5 cases were bilateral. Duplex system ureterocele was observed in 16 cases, all of which were unilateral. Clinical manifestations: urinary tract infection in 13 cases, 11 cases of ureterocele or hydronephrosis and ureteral dilation were found during antenatal examination, and 4 cases of ureterocele were found after birth. Urological ultrasound, intravenous pyelography(IVP) and voiding cystourethrography(VCUG) were performed in all children, and 17 cases underwent magnetic resonance urolography (MRU), and confirm the diagnosis of ureterocele preoperatively. All of the cases were performed the transurethral incision.The ureterocele was punctured and incised 1-2 mm at the base of the bulge, and 2-4 points were punctured according to the bulge atrophy. Bilateral ureteroceles were punctured and incised simultaneously. Postoperative urine routine test, urinary tract color ultrasound and VCUG were performed to determine if there is urinary tract infection, hydronephrosis, ureteral dilation and bulging, and whether a second surgery is needed.Results:All operations were conducted successfully. The intraoperative bleeding was less than 3 ml and no intraoperative complications. The operative time was (28.4±10.3) min. The median postoperative follow-up was 34 (32, 36) months. Six cases underwent postoperative VCUG examination. Eleven children were recovered well with single systemic ureterocele. One child developed grade Ⅳ vesicoureteral reflux(VUR)and combined with bladder diverticulum, and ureterocele underwent open diverticulotomy and ureteral reimplantation six months after surgery. Nine children were recovered well with duplex systemic ureterocele. Six cases of children developed infection, of which 2 cases had an infection once within one month after TUI, and the other four cases still had intermittent infections after six months and VCUG was performed, and one case showed grade Ⅲ VUR of the lower ureter, which was observed conservatively, while the other three cases had enlarged cysts but no VUR, and upper heminephrectomy was performed, and the patients recovered well after surgery. Except for these 6 exceptions, in another case, after ten years of follow-up, the ureterocele became larger but no VUR, and the results were good after a second transurethral incision. There was no significant difference in the postoperative infections, new VUR cases, and secondary surgeries between the two groups.Conclusions:Transurethral incision has good surgical effect on children with single system ureterocele and duplex system ureterocele, and has advantages of easy operation, less trauma, safety and effectiveness, and few complications. It deserves to be recommended as the treatment of choice, especially for infants and young children.

Objective:To investigate the clinical application effect of enhanced recovery after surgery(ERAS) in the perioperative period of primary repair for children with hypospadias.Methods:Non-randomized controlled study.Retrospective analysis was made on clinical data of 206 children with hypospadias admitted to the Department of Urology, Shanxi Children′s Hospital from March 2018 to March 2022.According to whether the concept of ERAS was adopted for perioperative management of children, they were divided into the ERAS group(109 cases) and the non-ERAS group(97 cases). t-test and Chi-square test were used to analyze the differences between the two groups of patients in hospitalization days, hospitalization costs, pain scores on the first day after surgery, average number of bowel movements within 5 days after surgery, first out-of-bed activity time, hospital satisfaction score, and complication rate. Results:Pediatric patients in the ERAS group showed better outcomes compared to the non-ERAS group: shorter hospital stays[(7.71±1.12) d vs.(21.00±1.07) d], lower hospitalization costs[(10 043.21±1 341.00) yuan vs.(12 993.44±1 081.00) yuan], lower postoperative pain scores on the first day[(5.21±1.32) points vs.(6.09±1.07) points], more frequent bowel movements within 5 days[(5.16±0.65) times vs.(2.91±0.48) times], earlier time to first out-of-bed activity[(5.03±0.61) d vs.(7.12±0.57) d], and higher hospital satisfaction scores[(4.71±0.21) points vs.(4.14±0.15) points], and the differences were statistically significant(all P<0.05).Additionally, the ERAS group had lower rates of fever(6.42%, 7/109) and constipation(3.67%, 4/109) before urinary catheter removal compared to the non-ERAS group[21.64%(21/97) and 28.87%(28/97), respectively](all P<0.05).There were no significant differences in the incidences of complications such as urethral prolapse, infection, delayed wound healing, and bleeding, as well as urethral stricture, urethral fistula, and urethral diverticulum after urinary catheter removal between the two groups(all P>0.05). Conclusions:ERAS protocol applied in the perioperative period of primary repair for children with hypospadias can shorten the hospitalization time, lower the hospitalization costs, and accelerate the rehabilitation of children.It is worth further promotion.

Objective:To investigate the high-resolution CT features and risk factors of secondary bronchiolitis obliterans (BO) in children with adenovirus pneumonia.Methods:In this study, a case-control study method was adopted, and 44 children with BO secondary to adenovirus pneumonia in Dongguan Children′s Hospital Affiliated to Guangdong Medical University from January 2015 to October 2020 were selected as the observation group, and 45 children with simple adenovirus pneumonia during the same period were selected as the control group. The differences in the chest high-resolution CT imaging characteristics of the two groups of children were compared. The risk factors of secondary BO in children with adenovirus pneumonia were analyzed by single factor and multiple factor logistic regression.Results:In the lung CT examination of children in the observation group, the detection rates of mosaic perfusion sign, bronchial wall thickening, bronchiectasis, lung consolidation and clear lung were significantly higher than those in the control group, and the difference was statistically significant (all P<0.05); Logistic regression model showed that prolonged heat course, high heat peak, mechanical ventilation treatment and prolonged mechanical ventilation time were independent risk factors of secondary BO children with adenovirus pneumonia (all P<0.05). Conclusions:Children with BO secondary to adenovirus pneumonia have typical high-resolution CT features, which is of high practical value for clinical diagnosis. Prolonged heat course, high heat peak, mechanical ventilation treatment and prolonged mechanical ventilation were independent risk factors of secondary BO in children with adenovirus pneumonia.

Neurons in the primary auditory area (AUDp) innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions. However, the brain-wide connections of these neurons have not been comprehensively investigated. Here, we simultaneously applied virus-based anterograde and retrograde tracing, labeled the connections of excitatory and inhibitory neurons in the mouse AUDp, and acquired whole-brain information using a dual-channel fluorescence micro-optical sectioning tomography system. Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions. In the isocortex, functionally different areas consistently sent feedback-dominated projections to these neurons, with concomitant laterally-dominated projections from the sensory and limbic cortices to inhibitory neurons. In subcortical regions, the dorsal and medial parts of the non-lemniscal auditory thalamus (AT) were reciprocally connected to the AUDp, while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back, indicating the regional heterogeneity of the AUDp-AT circuit. Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Abdominoscrotal hydrocele is rare in clinic. In the past, routine examination and diagnosis were difficult, easy to be misdiagnosed. The daily operations were mostly completed through the groin area or abdominal incision, the wound is large. The application of laparoscopy can clearly diagnose the abdominoscrotal hydrocele through "springing back ball" sign, and can cure the disease by laparoscopic resection of interperitoneal mass and closure of the internal ring. It is worthy of clinical application. In this article, we summarized and analyzed the clinical experience of 15 cases of children with abdominoscrotal hydrocele diagnosed and treated by laparoscopy, to explore the value of the laparoscopic technology in the diagnosis and treatment of the abdominoscrotal hydrocele.