Objective:To explore the application value of transpubic access on female urogenital tract injury.Methods:A retrospective analysis was conducted on 15 female patients with urogenital tract injury caused by trauma admitted to our department from May 2020 to October 2024，all of whom were complicated urethral stricture or atresia，accompanied by urethrovaginal fistula or vaginorectal fistula. All patients underwent suprapubic vesicostomy before surgery，and 1 case underwent sigmoidostomy simultaneously. The mean age of the patients was（29.6 ± 3.2）years old，and the course of disease was 6-24 months. Preoperative urethrography and urethroscope showed the location of urethral stenosis，with proximal urethra stricture in 7 cases and distal urethra stricture in 8 cases. The average length of strictures was（2.8±0.2）cm. The urethral ultrasonography，magnetic resonance and CTU examination showed 8 patients were complicated with urethrovaginal fistula，and 1 patient was complicated with vaginorectal fistula. All patients underwent transpubic access and resection of symphysis pubis. According to the specific conditions of urethral stricture，7 of them underwent end-to-end urethral anastomosis，5 cases underwent bladder wall flap urethroplasty，3 cases underwent vulva flap urethroplasty，8 cases underwent urethral vaginal fistula repair，1 case underwent vagino-rectal fistula repair，and 7 cases underwent vaginoplasty during the operation.Results:All the 15 patients underwent successful operation without complication. After the catheter being removed 4 weeks after surgery，2 patients had urgent urinary incontinence and 3 patients had stress urinary incontinence. The bladder neck was reconstructed 3 months after surgery，the symptoms of urinary incontinence improved in 1 case，urinary incontinence remained in 2 cases，and pharmaceutical or physical therapy were continued. Two patients could not urinate normally after the catheter was removed and still carried the vesicostomy tube，waiting for further treatment. The other 8 patients had unobtrusive voiding after extubating，and were followed up for an average of（22.5±3.2）months. There was no recurrence of urinary fistula，and the average maximum urinary flow rate was（22.8±3.2）ml/s.Conclusions:The transpubic approach is a safe and effective way to treat female genital tract injury by different surgical methods according to specific conditions，especially for patients with severe trauma，poor local tissue conditions，complicated urethrovaginal fistula or vagino-rectal fistula.

Objective:To explore the application value of transpubic access on female urogenital tract injury.Methods:A retrospective analysis was conducted on 15 female patients with urogenital tract injury caused by trauma admitted to our department from May 2020 to October 2024，all of whom were complicated urethral stricture or atresia，accompanied by urethrovaginal fistula or vaginorectal fistula. All patients underwent suprapubic vesicostomy before surgery，and 1 case underwent sigmoidostomy simultaneously. The mean age of the patients was（29.6 ± 3.2）years old，and the course of disease was 6-24 months. Preoperative urethrography and urethroscope showed the location of urethral stenosis，with proximal urethra stricture in 7 cases and distal urethra stricture in 8 cases. The average length of strictures was（2.8±0.2）cm. The urethral ultrasonography，magnetic resonance and CTU examination showed 8 patients were complicated with urethrovaginal fistula，and 1 patient was complicated with vaginorectal fistula. All patients underwent transpubic access and resection of symphysis pubis. According to the specific conditions of urethral stricture，7 of them underwent end-to-end urethral anastomosis，5 cases underwent bladder wall flap urethroplasty，3 cases underwent vulva flap urethroplasty，8 cases underwent urethral vaginal fistula repair，1 case underwent vagino-rectal fistula repair，and 7 cases underwent vaginoplasty during the operation.Results:All the 15 patients underwent successful operation without complication. After the catheter being removed 4 weeks after surgery，2 patients had urgent urinary incontinence and 3 patients had stress urinary incontinence. The bladder neck was reconstructed 3 months after surgery，the symptoms of urinary incontinence improved in 1 case，urinary incontinence remained in 2 cases，and pharmaceutical or physical therapy were continued. Two patients could not urinate normally after the catheter was removed and still carried the vesicostomy tube，waiting for further treatment. The other 8 patients had unobtrusive voiding after extubating，and were followed up for an average of（22.5±3.2）months. There was no recurrence of urinary fistula，and the average maximum urinary flow rate was（22.8±3.2）ml/s.Conclusions:The transpubic approach is a safe and effective way to treat female genital tract injury by different surgical methods according to specific conditions，especially for patients with severe trauma，poor local tissue conditions，complicated urethrovaginal fistula or vagino-rectal fistula.

OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

Objective:To investigate the treatment strategies for vesicovaginal fistula（VVF）in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches：Group A（11 patients）：Underwent prone-position VVF repair. Mean age：（50.0±9.6）years；mean radiotherapy sessions：（22.6±2.2）. All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them，1 patient previously received laparoscopic VVF repair，1 transvaginal VVF repair，and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery，the average daily usage of urine pads was 16.7（12.8，25.7）pieces，and the quality of life（QOL）score stood at 4.0（4.0，5.0）points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder，while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.2（0.8，1.6）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 3 cases of type 1，4 cases of type 2，2 cases of type 3，and 2 cases of type 4；7 cases of type A and 4 cases of type B；as well as 3 cases of typeⅠ，7 cases of type Ⅱ，and 1 case of type Ⅲ.Group B（20 patients）：Underwent gracilis muscle flap packing for VVF repair. Mean age：（58.6±8.8）years；mean radiotherapy sessions：（29.8±3.9）. Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions：3 had laparoscopic VVF repair，4 transvaginal VVF repair，and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery，the average daily usage of urine pads was 19.7（15.8，27.7）pieces，and the QOL score stood at 5.0（5.0，6.0）points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder，while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.8（1.0，3.2）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 4 cases of type 1，9 cases of type 2，3 cases of type 3，and 4 cases of type 4；6 cases of type A，11 cases of type B and 3 cases of type C；as well as 1 cases of type Ⅱ，and 19 case of type Ⅲ. Group C（2 patients）：Underwent ureterocutaneous diversion. Ages：67 and 73 years；radiotherapy sessions：51 and 60，respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery，the daily usage of urine pads was 29 and 23 pieces，respectively，and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder，with diameters of 3 cm and 4 cm，respectively. Additionally，partial defects were noted in the ventral wall of the urethra，while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas，both cases were categorized as type 4，type C，and type Ⅲ. For Groups A and B，urinary catheters were indwelled for 3 weeks postoperatively，then removed to assess spontaneous urination and incontinence. QOL was evaluated，with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence，re-repair was performed 3?6 months later based on patient preference. For Group C，double-J stents were placed in the ureters，and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months，with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C，surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A：Follow-up duration：16.3（9.6，24.6）months. Surgical repair succeeded in 7 patients，with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence：2 refused further treatment，and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired，while one recurrence case refused further treatment. Group B：Follow-up duration：17.0（9.5，24.8）months（8?32 months）. Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence：5 refused further surgery，and 2 underwent re-repair. One repair succeeded without incontinence，while one recurrence case refused treatment. Group C：Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence（no urine pads needed），and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3，respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general，patients who are younger，have received lower doses of radiation therapy，present with smaller fistula diameters，have well-vascularized and elastic perifistular tissues，and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair，have a history of at least two previous repair attempts，or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas，extensive pale and inelastic perifistular tissues，and who are not amenable to repair surgery undergo ureterocutaneous diversion.

Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.

Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective:To investigate the clinical effect of transposition of gracilis muscle flap in repairing urethral perineal fis-tula after Miles operation.Methods:The clinical data of 3 patients with urethral perineal fistula treated in the Second Affiliated Hos-pital of Zhejiang University from September 2023 to November 2024 were analyzed retrospectively.All patients were male,aged from 59 to 68 years(mean 63 years).All patients underwent Miles operation because of low rectal cancer.Urethral perineal fistula occurred after 2 months to 13 years of the operation.The underlying comorbidities included diabetes(2/3),preoperative chemoradiotherapy(1/3),and chemotherapy alone(1/3).The endourethral fistula was located in the apical and membranous part of the prostate,with a diameter of 1.5-2.0 cm and a mean of 1.7 cm.Suprapubic cystostomy was performed one month before operation.In all 3 cases,perineal inverted"Y"incision was taken under general anesthesia to expose urethral fistula,cut off necrotic tissue and suture urethral fistula.The gracilis muscle of the right thigh was taken and turned through the perineal subcutaneous tunnel.and 6 stitches were suture at the urethral fistula.Results:The operations of all 3 patients were completed successfully.The follow-up period ranged from 2 months to 12 months,with an average of 8 months.There was no case of urinary incontinence after removal of catheter 3 weeks after operation.In two patients,urethrography was reviewed 1 month after surgery to show no fistula residue and urethral stenosis,and the fistula was removed.In one patient with a history of radiotherapy,urethrography was reviewed 1 month after surgery to show a small amount of contrast overflow around the urethra,and urethrography was reviewed again 3 months after surgery to show no contrast over-flow around the urethra.All the 3 patients had no disturbance of movement of the right lower limb,and the pain of different degrees of thigh incision was acceptable and basically relieved half a month after operation.Conclusion:Gracilis muscle flap is one of the ef-fective methods for repairing urethral perineal fistula after Miles operation,which has a precise surgical result and few complications.

Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective:To investigate the treatment strategies for vesicovaginal fistula（VVF）in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches：Group A（11 patients）：Underwent prone-position VVF repair. Mean age：（50.0±9.6）years；mean radiotherapy sessions：（22.6±2.2）. All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them，1 patient previously received laparoscopic VVF repair，1 transvaginal VVF repair，and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery，the average daily usage of urine pads was 16.7（12.8，25.7）pieces，and the quality of life（QOL）score stood at 4.0（4.0，5.0）points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder，while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.2（0.8，1.6）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 3 cases of type 1，4 cases of type 2，2 cases of type 3，and 2 cases of type 4；7 cases of type A and 4 cases of type B；as well as 3 cases of typeⅠ，7 cases of type Ⅱ，and 1 case of type Ⅲ.Group B（20 patients）：Underwent gracilis muscle flap packing for VVF repair. Mean age：（58.6±8.8）years；mean radiotherapy sessions：（29.8±3.9）. Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions：3 had laparoscopic VVF repair，4 transvaginal VVF repair，and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery，the average daily usage of urine pads was 19.7（15.8，27.7）pieces，and the QOL score stood at 5.0（5.0，6.0）points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder，while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.8（1.0，3.2）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 4 cases of type 1，9 cases of type 2，3 cases of type 3，and 4 cases of type 4；6 cases of type A，11 cases of type B and 3 cases of type C；as well as 1 cases of type Ⅱ，and 19 case of type Ⅲ. Group C（2 patients）：Underwent ureterocutaneous diversion. Ages：67 and 73 years；radiotherapy sessions：51 and 60，respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery，the daily usage of urine pads was 29 and 23 pieces，respectively，and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder，with diameters of 3 cm and 4 cm，respectively. Additionally，partial defects were noted in the ventral wall of the urethra，while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas，both cases were categorized as type 4，type C，and type Ⅲ. For Groups A and B，urinary catheters were indwelled for 3 weeks postoperatively，then removed to assess spontaneous urination and incontinence. QOL was evaluated，with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence，re-repair was performed 3?6 months later based on patient preference. For Group C，double-J stents were placed in the ureters，and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months，with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C，surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A：Follow-up duration：16.3（9.6，24.6）months. Surgical repair succeeded in 7 patients，with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence：2 refused further treatment，and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired，while one recurrence case refused further treatment. Group B：Follow-up duration：17.0（9.5，24.8）months（8?32 months）. Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence：5 refused further surgery，and 2 underwent re-repair. One repair succeeded without incontinence，while one recurrence case refused treatment. Group C：Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence（no urine pads needed），and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3，respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general，patients who are younger，have received lower doses of radiation therapy，present with smaller fistula diameters，have well-vascularized and elastic perifistular tissues，and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair，have a history of at least two previous repair attempts，or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas，extensive pale and inelastic perifistular tissues，and who are not amenable to repair surgery undergo ureterocutaneous diversion.