Objective Pelvic fracture urethral distraction defect(PFUDD)is relatively rare among boys and difficult to manage.This study aims to explore the efficacy of progressive urethral anastomosis in the treatment of this disease.Methods A total of 34 male children with PFUDD who were admitted to our hospitals during Jan.2008 and Dec.2022 were collected.The therapeutic effects and the occurrence of postoperative complications were observed and analyzed.Results All cases were traumatic pelvic fractures,including fall injuries in 3 cases,traffic-related impact injuries in 21 cases,and pelvic crush injuries in 10 cases.Urethroplasty was performed at least 3 months after the initial trauma or after the failure of the last intervention.The mean length of the urethral defect was 3.0 cm,with a range of 1.5 to 5.5 cm.Three cases complicated with urethrorectal fistula underwent urethroplasty concomitant with fistula repair.All children were followed up for an average of 65.5 months,with a range of 5.0 to 155.0 months,with 32 cases(94.1％)achieving successful treatment.Two cases with stricture recurrence were cured by a second operation.Three cases with mild urinary incontinence were improved after half a year of pelvic floor muscle rehabilitation training.Conclusion The progressive urethral anastomosis strategy can yield a relatively high success rate.The trans-inferior-pubic resection or simpler approaches can be adopted for the treatment of PFUDD in over 90％of male children.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

Objective Pelvic fracture urethral distraction defect(PFUDD)is relatively rare among boys and difficult to manage.This study aims to explore the efficacy of progressive urethral anastomosis in the treatment of this disease.Methods A total of 34 male children with PFUDD who were admitted to our hospitals during Jan.2008 and Dec.2022 were collected.The therapeutic effects and the occurrence of postoperative complications were observed and analyzed.Results All cases were traumatic pelvic fractures,including fall injuries in 3 cases,traffic-related impact injuries in 21 cases,and pelvic crush injuries in 10 cases.Urethroplasty was performed at least 3 months after the initial trauma or after the failure of the last intervention.The mean length of the urethral defect was 3.0 cm,with a range of 1.5 to 5.5 cm.Three cases complicated with urethrorectal fistula underwent urethroplasty concomitant with fistula repair.All children were followed up for an average of 65.5 months,with a range of 5.0 to 155.0 months,with 32 cases(94.1％)achieving successful treatment.Two cases with stricture recurrence were cured by a second operation.Three cases with mild urinary incontinence were improved after half a year of pelvic floor muscle rehabilitation training.Conclusion The progressive urethral anastomosis strategy can yield a relatively high success rate.The trans-inferior-pubic resection or simpler approaches can be adopted for the treatment of PFUDD in over 90％of male children.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

ObjectiveTo observe the clinical efficacy and mechanism of Tongnao Yizhi Formula （通脑益智方， TYF） in treating vascular cognitive impairment no dementia （VCIND） with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome. MethodsNinety-two VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome were randomly divided into control group （42 cases） and treatment group （52 cases）. Both groups received routine basic treatment. The control group was given donapezil hydrochloride capsules orally， 5 mg each time， once at night， while the treatment group was given TYF orally， 1 dose per day. Both groups were treated continuously for 3 months. The scores of Mini-Mental State Examination （MMSE）， Vascular Dementia Assessment Scale-Cognitive Subscale （VaDAS-Cog）， Activity of Daily Living Scale （ADL）， and TCM syndrome scores （the primary symptoms such as sluggish thinking， forgetfulness， temperament changes， and language confusion， and secondary symptoms such as weakness of waist and knees， dizziness and headache， occasional tinnitus， fatigue， heaviness of limbs， insomnia and irritability， poor appetite and abdominal distension， numbness of face） were observed before and after treatment in both groups. The changes in gut microflora diversity and flora abundance structure as well as fecal short-chain fatty acids （SCFAs） levels including acetic acid， propionic acid， butyric acid， isobutyric acid， isovaleric acid， valeric acid， and caproic acid were compared between groups. The feces of 20 healthy subjects in the same period were included as reference. Safety was evaluated during the study. ResultsAfter treatment， both groups exhibited significant increases in MMSE scores and decreases in VaDAS-cog scores （P＜0.05 or P＜0.01）， and ADL scores in the treatment group significantly increased （P＜0.05）. Scores of symptoms including sluggish thinking， forgetfulness， temperament change， language confusion， heaviness of limbs， insomnia， irritability， poor appetite， abdominal distension， and facial numbness as well as the total score significantly decreased in both groups after treatment （P＜0.05 or P＜0.01）. When compared between groups， the treatment group showed substantial reductions in scores of weakness of waist and knees， tinnitus， fatigue， heaviness of limbs， insomnia， irritability， loss of appetite and abdominal distension （P＜0.05 or P＜0.01）. The gut microflora diversity analysis showed that the Shannon index of the treatment group significantly increased after treatment （P＜0.05）.PCoA analysis and ANOSIM test indicated significant differences between groups， suggesting changes in microflora species （P＜0.01）. After treatment， the relative abundance of Bacteroidetes and Fusobacteria in the treatment group increased， while the relative abundance of Actinobacteria， Verrucomicrobia and Cyanobacteria decreased （P＜0.05）； the relative abundance of Faecalibacterium prausnitzii， Bifidobacterium， Lactobacillus， and Ruminococcus increased significantly （P＜0.05）. Compared to the the gut microflora species diversity of the healthy people， it is indicated that the gut microflora structure in the treatment group was close to that of the healthy people， while there was no such trend in the control group. In the treatment group， acetic acid， propionic acid， and butyric acid in the treatment group were all higher after treatment （P＜0.05 or P＜0.01）. ConclusionsTYF can improve the cognitive ability and quality of life of VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome， and this improvement may be related to regulating intestinal microecology.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.METH-ODS The concentrations of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine were determined by UPLC.The effects of temperature,perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods,the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC,and DAS 2.0 software was used to process the data.RESULTS The recovery rate of the probe increased with increasing temperature,and the higher the flow rate,the lower the recovery rate.The pharmacokinetic parameters of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine in microemulsion Cmax were(3.24±0.39)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1,respectively,and in AUC0-∞ were(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·mg·mL-1,respectively.CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microe-mulsion after transdermal administration,which provides a reference for the follow-up investigation and application of crossbow microe-mulsion.

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.

Objective:To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI.Methods:A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. Results:A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1- Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1- Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio ( OR) = 1.096, 95% confidence interval (95% CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients ( OR = 1.074, 95% CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95% CI was 0.611-0.694) and 0.593 (95% CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L ( OR = 2.772, 95% CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L ( OR = 2.511, 95% CI was 1.378-4.574, P = 0.003). Conclusions:Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.