1.Modified Xiaoyaosan Alleviates Neuronal Dysfunction in Rat Model of Post-myocardial Infarction Depression by Regulating Mitochondrial Quality Control Through Drp1/PINK1/Parkin Signaling Pathway
Zhen ZHONG ; Dongsheng WEI ; Xinyue XIONG ; Lin LI ; Mingli YAO ; Xinnuan SHI ; Youming JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):20-31
ObjectiveTo investigate the effects of modified Xiaoyaosan (JJXYS) on behavioral abnormalities and hippocampal mitochondrial quality control (MQC) in the rat model of post-myocardial infarction depression (PMD) and preliminarily explore its potential mechanism. MethodsA rat model of PMD was established by left anterior descending coronary artery ligation combined with chronic unpredictable mild stress (CUMS). Rats were randomized into a control group, a model group, a fluoxetine (FLX, 10 mg·kg-1) group, and low-, medium-, and high-dose JJXYS (JJXYS-L/M/H, 1.12, 2.24, 4.48 g·kg-1, respectively) groups. Depressive-like behaviors were evaluated by body weight monitoring, sucrose preference test, open field test, and forced swimming test. Hematoxylin-eosin staining and Nissl staining were used to observe hippocampal histomorphology and neuronal changes. Enzyme-linked immunosorbent assay was conducted to determine the serum levels of 5-hydroxytryptamine (5-HT), dopamine (DA), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The mRNA levels of MQC-related genes including peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factor 1 (Nrf1), and transcription factor A, mitochondrial (TFAM) in the hippocampal tissue were measured by real-time PCR. The expression of proteins related to the dynamin-related protein 1 (Drp1)/PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway was determined by Western blot. ResultsCompared with the control group, the model group showed restricted body weight gain, aggravated depressive-like behaviors, declined serum 5-HT and DA levels, evident hippocampal neuronal damage and reduced Nissl bodies, as well as downregulated expression of MQC-related genes and proteins (P<0.05). Compared with the model group, both FLX and JJXYS alleviated the above changes to varying degrees. Moreover, the JJXYS-M and JJXYS-H groups showed more pronounced effects, improving behavioral performance, restoring 5-HT and DA levels, alleviating hippocampal pathological injury, and upregulating the expression of PGC-1α/Nrf1/TFAM mRNA and Drp1/PINK1/Parkin signaling pathway-related proteins (P<0.05). ConclusionJJXYS can significantly alleviate depressive-like behaviors and neurotransmitter imbalance in the rat model of PMD by regulating hippocampal MQC and upregulating the Drp1/PINK1/Parkin-related pathway. This study provides experimental evidence for the intervention of PMD with JJXYS.
2.Posterior minimally invasive surgery for treating paralytic scoliosis with pelvic obliquity in children following spinal cord injury
Yi CHEN ; Xiaodong QIN ; Zhong HE ; Zhen LIU ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU
Chinese Journal of Orthopaedics 2025;45(2):67-76
Objective:To compare the clinical efficacy of Minimally Invasive Surgery (MIS) and traditional Posterior Spinal Fusion (PSF) in treating children with paralytic scoliosis with pelvic obliquity (PSPO) following spinal cord injury.Methods:A retrospective analysis was conducted on the data of 25 patients with PSPO who underwent surgical treatment at the Drum Tower Hospital affiliated with Nanjing University Medical School from January 2017 to June 2023. The cohort included 4 males and 21 females, aged 12.3±2.8 years (range 9-14 years). Patients were divided into the MIS group (12 cases) and the PSF group (13 cases). Radiological parameters were measured preoperatively, postoperatively, and at the last follow-up. Surgical time, intraoperative blood loss, intraoperative blood transfusion volume, length of hospital stay, total hospitalization costs, and complications were recorded. The Scoliosis Research Society questionnaires-22 (SRS-22) Chinese version were used to assess patient satisfaction and efficacy.Results:There were no statistically significant differences between the MIS and PSF groups in age, gender, Risser sign, preoperative Cobb angle for scoliosis, pelvic tilt angle, or local kyphosis angle ( P>0.05). The MIS group demonstrated surgical time of 176±30 minutes, intraoperative blood loss of 300±70 ml, blood transfusion volume of 280±175 ml, and total hospitalization costs of 87'800± 13'300 yuan, all of which were lower than PSF group, with values of 280±91 minutes, 1'433±116 ml, 1'351±996 ml, and 14'8400±26'100 yuan, respectively. These differences were statistically significant ( t=3.789, P=0.001; t=29.328, P<0.001; t=3.667, P=0.001; t=7.271, P<0.001). In the MIS group, preoperative, postoperative, and last follow-up Cobb angles were 79.11°±6.74°, 35.86°±4.98°, and 36.27°±4.84° respectively; pelvic tilt angles were 24.79°±5.58°, 9.18°±3.32°, and 8.79°±2.94°; local kyphosis angles were 38.84°±4.18°, 12.96°±4.87°, and 11.43°±6.08°, respectively. Postoperative and last follow-up angles were significantly reduced compared to preoperative values, with statistically significant differences ( P<0.05). In the PSF group, preoperative, postoperative, and last follow-up Cobb angles were 82.06°±9.26°, 34.75°±5.14°, and 35.15°±5.04° respectively; pelvic tilt angles were 26.60°±6.21°, 10.12°±3.21°, and 9.91°±2.97°; local kyphosis angles were 40.92°±7.04°, 10.92°±7.26°, and 14.02°±5.58°, respectively. Differences from preoperative to postoperative measurements were statistically significant ( P<0.05). At the last follow-up, both groups showed no significant loss of scoliosis correction, and there were no statistically significant differences between the groups postoperatively or at the last follow-up ( P>0.05). In the MIS group, one case of superficial surgical site infection and one case of postoperative atelectasis occurred. In the PSF group, two cases of deep surgical site infection, one case of poor screw placement, and two cases were transferred to the ICU postoperatively due to excessive intraoperative bleeding. Preoperative SRS-22 total scores were 2.0±0.6 for PSF and 2.1±0.4 for MIS. Postoperative SRS-22 total scores (excluding satisfaction) were 3.0±0.5 for PSF and 2.9±0.3 for MIS. The within-group differences from preoperative to postoperative were statistically significant ( P<0.05), while the between-group differences from preoperative to postoperative were not statistically significant ( P>0.05). Conclusion:Compared to the PSF technique, MIS can shorten surgery time, reduce intraoperative blood loss and perioperative complications, and decrease hospitalization costs. MIS can achieve similar early clinical efficacy.
3.Development of a visualizable machine learning model for mechanical complication risk in adult spinal deformity surgery
Jie LI ; Zhen TIAN ; Zhong HE ; Xiaodong QIN ; Jun QIAO ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU ; Zhen LIU
Chinese Journal of Orthopaedics 2025;45(17):1137-1146
Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.
4.Comparison between sinking and floating fresh Rehmanniae Radix samples by UHPLC-Q-Orbitrap HRMS, fingerprinting, and chemometrics.
Shi-Long LIU ; Hong-Wei ZHANG ; Zhen-Ling ZHANG ; Han-Ting JIA ; Zhi-Jun GUO ; Rui-Sheng WANG ; Hong-Wei ZHANG ; Shuo WANG ; Yi-Jian ZHONG
China Journal of Chinese Materia Medica 2025;50(14):3918-3929
This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Rehmannia/chemistry*
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Chemometrics
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Mass Spectrometry/methods*
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Quality Control
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Principal Component Analysis
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Plant Extracts
5.Posterior minimally invasive surgery for treating paralytic scoliosis with pelvic obliquity in children following spinal cord injury
Yi CHEN ; Xiaodong QIN ; Zhong HE ; Zhen LIU ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU
Chinese Journal of Orthopaedics 2025;45(2):67-76
Objective:To compare the clinical efficacy of Minimally Invasive Surgery (MIS) and traditional Posterior Spinal Fusion (PSF) in treating children with paralytic scoliosis with pelvic obliquity (PSPO) following spinal cord injury.Methods:A retrospective analysis was conducted on the data of 25 patients with PSPO who underwent surgical treatment at the Drum Tower Hospital affiliated with Nanjing University Medical School from January 2017 to June 2023. The cohort included 4 males and 21 females, aged 12.3±2.8 years (range 9-14 years). Patients were divided into the MIS group (12 cases) and the PSF group (13 cases). Radiological parameters were measured preoperatively, postoperatively, and at the last follow-up. Surgical time, intraoperative blood loss, intraoperative blood transfusion volume, length of hospital stay, total hospitalization costs, and complications were recorded. The Scoliosis Research Society questionnaires-22 (SRS-22) Chinese version were used to assess patient satisfaction and efficacy.Results:There were no statistically significant differences between the MIS and PSF groups in age, gender, Risser sign, preoperative Cobb angle for scoliosis, pelvic tilt angle, or local kyphosis angle ( P>0.05). The MIS group demonstrated surgical time of 176±30 minutes, intraoperative blood loss of 300±70 ml, blood transfusion volume of 280±175 ml, and total hospitalization costs of 87'800± 13'300 yuan, all of which were lower than PSF group, with values of 280±91 minutes, 1'433±116 ml, 1'351±996 ml, and 14'8400±26'100 yuan, respectively. These differences were statistically significant ( t=3.789, P=0.001; t=29.328, P<0.001; t=3.667, P=0.001; t=7.271, P<0.001). In the MIS group, preoperative, postoperative, and last follow-up Cobb angles were 79.11°±6.74°, 35.86°±4.98°, and 36.27°±4.84° respectively; pelvic tilt angles were 24.79°±5.58°, 9.18°±3.32°, and 8.79°±2.94°; local kyphosis angles were 38.84°±4.18°, 12.96°±4.87°, and 11.43°±6.08°, respectively. Postoperative and last follow-up angles were significantly reduced compared to preoperative values, with statistically significant differences ( P<0.05). In the PSF group, preoperative, postoperative, and last follow-up Cobb angles were 82.06°±9.26°, 34.75°±5.14°, and 35.15°±5.04° respectively; pelvic tilt angles were 26.60°±6.21°, 10.12°±3.21°, and 9.91°±2.97°; local kyphosis angles were 40.92°±7.04°, 10.92°±7.26°, and 14.02°±5.58°, respectively. Differences from preoperative to postoperative measurements were statistically significant ( P<0.05). At the last follow-up, both groups showed no significant loss of scoliosis correction, and there were no statistically significant differences between the groups postoperatively or at the last follow-up ( P>0.05). In the MIS group, one case of superficial surgical site infection and one case of postoperative atelectasis occurred. In the PSF group, two cases of deep surgical site infection, one case of poor screw placement, and two cases were transferred to the ICU postoperatively due to excessive intraoperative bleeding. Preoperative SRS-22 total scores were 2.0±0.6 for PSF and 2.1±0.4 for MIS. Postoperative SRS-22 total scores (excluding satisfaction) were 3.0±0.5 for PSF and 2.9±0.3 for MIS. The within-group differences from preoperative to postoperative were statistically significant ( P<0.05), while the between-group differences from preoperative to postoperative were not statistically significant ( P>0.05). Conclusion:Compared to the PSF technique, MIS can shorten surgery time, reduce intraoperative blood loss and perioperative complications, and decrease hospitalization costs. MIS can achieve similar early clinical efficacy.
6.Development of a visualizable machine learning model for mechanical complication risk in adult spinal deformity surgery
Jie LI ; Zhen TIAN ; Zhong HE ; Xiaodong QIN ; Jun QIAO ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU ; Zhen LIU
Chinese Journal of Orthopaedics 2025;45(17):1137-1146
Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.
7.Effects of GABA signaling pathway on endoplasmic reticulum stress and mitochondrial autophagy in septic rats with acute lung injury
Min ZHONG ; Zhen SHI ; Jinsong ZHOU ; Jinjie LI
Tianjin Medical Journal 2024;52(7):733-737
Objective To investigate the effect of γ-aminobutyric acid(GABA)signaling pathway on endoplasmic reticulum(ER)stress and mitochondrial autophagy in septic rats with acute lung injury(ALI).Methods SD rats were randomly grouped into the control(CON)group,the model group,the GABA signaling pathway activator Baclofen group(the Baclofen group),the GABA signaling pathway inhibitor dicentrine group(the BIC group),with 6 rats in each group.The Baclofen group received intraperitoneal injection of 5 mg/kg Baclofen,and the BIC group received intraperitoneal injection of 1 mg/kg BIC,once a day,for two consecutive weeks.The CON group and the model group were injected with an equal amount of physiological saline via intraperitoneal injection.Enzyme linked immunosorbent assay was applied to detect serum levels of superoxide dismutase(SOD)and malondialdehyde(MDA)and levels of cytochrome C(Cyt.C)and Nicotinamide adenine dinucleotide phosphate(NADPH)in bronchoalveolar lavage fluid(BALF).Transmission electron microscopy(TEM)was applied to observe the ultrastructure of lung tissue cells.HE staining was applied to observe the pathological morphology of lung tissue.TUNEL staining was applied to observe the apoptosis of lung tissue.Western blot assay was applied to detect expression levels of GABAAR,GRP78 and CHOP proteins in lung tissue.Results Compared with the model group,the lung swelling,congestion and inflammatory cell infiltration were improved in the Baclofen group,and the lung injury score,MDA content,apoptosis index,Cyt.C and NADPH levels,GRP78,and CHOP protein levels were reduced(P<0.05).The number of autophagic vacuoles in phagocytic mitochondria,SOD content and GABAAR protein level were increased(P<0.05),however,the trend of above indicators in the BIC group was opposite to that in the Baclofen group.Conclusion Up-regulation of GABA signaling pathway may have an improvement effect on ALI in sepsis rats.
8.A survey on the management status and indicators of pathogen detection rate before antimicrobial treatment of inpatients in 265 medical institu-tions in Guangdong Province
Jia-jin CHEN ; Zhen-feng ZHONG ; Shi-yun WANG ; Ting HUANG ; Shu-xian CHEN ; Chen ZHU ; Yi-nan LI ; Li-li PENG ; Yuan-chun MO ; Min-shan CHEN ; Wei-qing LIN ; Xiu-juan QU ; Fang YU ; Zhi-xing LI ; Shu-mei SUN
Chinese Journal of Infection Control 2024;23(12):1499-1507
Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98%),developing special action improvement plans(79.01%),estab-lishing pathogen detection rate management systems(91.71%),and developing management assessment plans(76.80%)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P<0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P<0.05).The pathogen detection rate(61.07%)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00%)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P<0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P<0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.
9.A multicenter, randomized controlled clinical trial of Pseudomonas aeruginosa injection for prevention of recurrent urinary tract infections
Zhen DU ; Liang CUI ; Zhan GAO ; Yi ZHI ; Gang CUI ; Peng ZHANG ; Hongfeng GUO ; Shan ZHONG ; Benkang SHI ; Yan LI ; Yong ZHANG ; Yifei XING ; Shan CHEN ; Ludong QIAO
Chinese Journal of Urology 2024;45(12):925-931
Objective:To investigate the clinical efficacy and safety of Pseudomonas aeruginosa injection in preventing reurrent urinary tract infection in women. Methods:This was a multicenter, randomized, open, positive-controlled, non-inferiority trial involving female patients with recurrent urinary tract infections (rUTIs) who were admitted to 11 medical centers in China. Inclusion criteria: ①Aged 18-70 years, with verifiable clinical data showing at least 3 episodes of acute UTIs within 1 year and at least 2 episodes within 6 months, and cured by antimicrobial therapy; ② At the time of enrollment, the patients had no obvious symptoms of urinary tract irritation, normal white blood cell count in midstream urine routine (within the normal range of laboratory standards of each unit) or ≤3HP by centrifuge microscopy, negative leucocyte esterase and nitrite, and negative urine culture; ③No abnormal urinary anatomic function (such as urinary obstruction, calculus or congenital urinary malformation) and residual urine volume ≤50 ml were detected by B-ultrasound of urinary system; ④Informed consent signed by the person or agent; ⑤Clear consciousness, able to answer questions independently, according to the requirements of the test plan to complete the research questionnaire. Exclusion criteria: ①Patients allergic to the above drugs; ②Any complex signs of urinary tract infection or pyelonephritis (manifested as low back pain, fever ≥37.3℃, systemic symptoms); ③Drugs affecting immune function were used within 7 days before randomization; ④Patients with basic diseases of urinary system such as obstruction, calculus, urinary stenosis, vesicoureteral reflux or other functional abnormalities, urine diversion, indwelling catheter or stent tube or intermittent catheterization; ⑤Combined with or existing systemic lupus erythematosus, AIDS and other diseases that can lead to systemic immune function abnormalities; ⑥Patients who are known or suspected to be pregnant, breastfeeding, or planning a pregnancy within 3 months of stopping the drug; ⑦Patients with malignant tumors and mental patients; ⑧Persons who have received any other investigational drug treatment or participated in another interventional clinical trial within 4 weeks prior to screening; ⑨Failure to comply with the trial protocol or other conditions deemed unsuitable for enrollment by the investigator. Patients were randomly divided into 2 groups. The experimental group was given Pseudomonas aeruginosa injection for 5 times, 0.5 ml for the first time, and 1 ml/ time per week for the following 4 weeks. The control group was given fosfomycin aminotriol 3g orally, once every 10 days, for 9 consecutive times. The patients were followed up for 6 to 8 months, during which urinary tract symptoms developed and routine urine tests showed abnormally elevated white blood cells, which was defined as recurrent UTIs. Urine routine, liver and kidney function, and urinary secretory immunoglobulin A(SIgA) were reviewed 0-2 days (V2) after the 5th administration of the experimental group and the 4th administration of the control group. Urine routine and urine SIgA were reviewed at (90±10) d (V3) and (180±10) d (V4) after treatment. At (270±10) d (V5) after treatment, the recurrence (re-infection caused by the same species of bacteria) or re-infection (re-infection caused by non-same species of bacteria) of the two groups were compared, and non-inferiority analysis was performed, and the non-inferiority threshold was set at 0.2. Results:From March 2021 to May 2022, a total of 152 rUTIs patients were enrolled in this study, including 80 patients in the experimental group, 71 patients in the intention-to-analysis set (ITT) and 66 patients in the protocol analysis set (PPS). In the control group, 72 cases met ITT in 69 cases and PPS in 67 cases. There were no significant differences in age, body mass index, marital status, duration of urinary tract infection, history of diabetes, history of previous major surgery, history of infection, and urinary SIgA between the two groups (all P>0.05). The recurrence rates of the experimental group and the control group at V5 time point were 44.78% (30/67) and 42.65% (29/68), respectively ( P=0.803) (ITT data set analysis results showed that the difference in recurrence rates between the two groups was 0.0213(95% CI-0.1460-0.1886, P=0.0048). PPS data set analysis showed that the difference of recurrence rate between the two groups was -0.0021(95%CI -0.1711-0.1670, P=0.0109), and the recurrence rate of the experimental group was not worse than that of the control group. At V2 time points, there were no significant differences in liver and kidney function indexes between test group and control group ( P>0.05). At V2 to V4 time points, urinary SIgA of test group and control group were 0.90 (0.37, 2.89) mg/L and 1.32 (0.34, 3.08) mg/L, 1.54 (0.44, 3.23) mg/L and 1.71 (0.27, 2.92) mg/L, 1.11 (0.65, 3.42) mg/L and 2.18 (0.43, 3.26) mg/L, there was no statistical significance ( P>0.05). The incidence of adverse events in the experimental group was 30.0% (24/80), including 14 cases of redness, pain and discomfort at the injection site, 5 cases of fever, 2 cases of allergic rash, and 1 case of urticaria, headache and constipation each. The incidence of adverse events in the control group was 5.6% (4/72), all of which were diarrhea, and the difference between the two groups was statistically significant ( P<0.01). No life-threatening serious adverse events occurred in both groups, and all adverse events were self-healing without additional intervention. Conclusions:Compared with fosfomycin aminotriol, Pseudomonas aeruginosa injection has the same clinical effect in preventing rUTI and has good safety.
10.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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