Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

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 the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

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 explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

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 discuss the aeromedical support enhancement measures by analyzing the disease spectrum and the aeromedical characteristics of temporarily grounded flying personnel.Methods:A retrospective analysis was conducted on the clinical data of 244 flying personnel who received medical treatment at the Southern Theater Air Force Hospital from November 2011 to March 2023 and were temporarily grounded in aeromedical assessment. The flying personnel were grouped by aircraft types (fighter, trans-bomber, helicopter) and flying hours (<2 000 h and ≥2 000 h), and the spectrum of temporarily unqualified flight diseases were statistically analyzed. The disease distributions of flying personnel in different aircraft types and flying hours were compared.Results:Among the 244 flying personnel (389 person-time) who were identified as temporarily grounded by aeromedical assessment, the major specialties involved were surgery (52.5%), internal medicine (24.6%) and neuropsychiatry (14.3%). The top 10 diseases leading to temporarily grounded were cervical and lumbar spine diseases, anxiety-depression, knee joint injury (surgical treatment), anal fistula (surgical treatment), sleep disorders, joint and soft tissue injuries, hypertension, ureteral stones, achilles tendon rupture and fracture (conservative treatment). There was a significant difference in the proportion of flying personnel temporarily grounded due to anxiety-depression among different aircraft types ( P=0.014). There were no significant differences in other diseases among flying personnel in different aircraft types (all P>0.05). The proportion of temporarily grounded flying personnel due to knee joint injury in flying hours <2 000 h was higher than that in flying hours ≥2 000 h, and the difference was significant ( χ2=4.47, P=0.035). Among the 71 flying personnel who underwent repeated ground observation, 28 were identified as qualified, 22 were grounded and 21 were still temporarily grounded. Conclusions:The proportion of flying personnel temporarily grounded due to diseases is relatively high. Accurate diagnosis and treatment of diseases and aeromedical assessment are important links to promote the early return of flying personnel.

Objective:To discuss the aeromedical support enhancement measures by analyzing the disease spectrum and the aeromedical characteristics of temporarily grounded flying personnel.Methods:A retrospective analysis was conducted on the clinical data of 244 flying personnel who received medical treatment at the Southern Theater Air Force Hospital from November 2011 to March 2023 and were temporarily grounded in aeromedical assessment. The flying personnel were grouped by aircraft types (fighter, trans-bomber, helicopter) and flying hours (<2 000 h and ≥2 000 h), and the spectrum of temporarily unqualified flight diseases were statistically analyzed. The disease distributions of flying personnel in different aircraft types and flying hours were compared.Results:Among the 244 flying personnel (389 person-time) who were identified as temporarily grounded by aeromedical assessment, the major specialties involved were surgery (52.5%), internal medicine (24.6%) and neuropsychiatry (14.3%). The top 10 diseases leading to temporarily grounded were cervical and lumbar spine diseases, anxiety-depression, knee joint injury (surgical treatment), anal fistula (surgical treatment), sleep disorders, joint and soft tissue injuries, hypertension, ureteral stones, achilles tendon rupture and fracture (conservative treatment). There was a significant difference in the proportion of flying personnel temporarily grounded due to anxiety-depression among different aircraft types ( P=0.014). There were no significant differences in other diseases among flying personnel in different aircraft types (all P>0.05). The proportion of temporarily grounded flying personnel due to knee joint injury in flying hours <2 000 h was higher than that in flying hours ≥2 000 h, and the difference was significant ( χ2=4.47, P=0.035). Among the 71 flying personnel who underwent repeated ground observation, 28 were identified as qualified, 22 were grounded and 21 were still temporarily grounded. Conclusions:The proportion of flying personnel temporarily grounded due to diseases is relatively high. Accurate diagnosis and treatment of diseases and aeromedical assessment are important links to promote the early return of flying personnel.

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*