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 off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.

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.

Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To investigate off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.

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.

Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.

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.