1.Qingre Sanzhuo Decoction Treats Gouty Arthritis Combined with Hyperuricaemia in Rats via NLRP3/ASC/Caspase-1 Pathway
Haolin LI ; Qian BAI ; Weigang CHENG ; Weiqing LI ; Juanjuan YANG ; Peixin HE ; Huijun YANG ; Haidong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):49-57
ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis (GA) combined with hyperuricaemia (HUA). MethodsSixty male SD rats were randomized into normal, model, colchicine (0.5 mg·kg-1), and low-, medium-, and high-dose (17, 34, 68 g·kg-1, respectively) Qingre Sanzhuo decoction groups (n=10). The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid (SUA) in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5, 12, 24, 48 h after modeling, and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), C reactive protein (CRP), and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), gasdermin D (GSDMD), and nuclear factor-kappa B (NF-κB) in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3, ASC, and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group, the model group showed increased SUA in the serum (P<0.05), ankle joint swelling and joint inflammation (P<0.05), increased number of blood vessels in the synovium, inflammatory cell foci in the synovial bursa, elevated serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and up-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). Compared with the model group, the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum (P<0.05), alleviated ankle joint swelling and joint inflammation (P<0.05), lowered serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and down-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). However, in terms of ameliorating the pathological changes of ankle joints, only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines, such as TNF-α, IL-1β, CRP, and IL-18.
2.Antimicrobial resistance surveillance in the bacterial strains isolated from pediatric intensive care units in China:results from 2020 to 2022
Jing LIU ; Huiyuan YAN ; Gangfeng YAN ; Guoping LU ; Pan FU ; Chuanqing WANG ; Danqun JIN ; Wenjia TONG ; Chenyu ZHANG ; Jianli CHEN ; Yi LIN ; Jia LEI ; Yibing CHENG ; Qunqun ZHANG ; Kaijie GAO ; Yuanyuan CHEN ; Shufang XIAO ; Juan HE ; Li JIANG ; Huimin XU ; Yuxia LI ; Hanghai DING ; Hehe CHEN ; Yao ZHENG ; Qunying CHEN ; Ying WANG ; Hong REN ; Chenmei ZHANG ; Zhenjie CHEN ; Mingming ZHOU ; Yucai ZHANG ; Yiping ZHOU ; Zhenjiang BAI ; Saihu HUANG ; Lili HUANG ; Weiguo YANG ; Weike MA ; Qing MENG ; Pengwei ZHU ; Yong LI ; Yan XU ; Yi WANG ; Yanqiang DU ; Huijun CAI ; Bizhen ZHU ; Huixuan SHI ; Shaoxian HONG ; Yukun HUANG ; Meilian HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):303-311
Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2%)and gram-negative organisms(60.8%).The top three organisms were S.aureus(13.6%,1 453/10 688),A.baumannii(10.0%,1 067/10 688),and coagulase-negative Staphylococcus(9.9%,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1%,19.4%,8.8%,30.9%,67.4%,and 28.8%,respectively.Overall,more than 50%of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25%of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80%of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3%in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.
3.Comparative efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation
Xinnan CHENG ; Shuai LI ; Jiaojiao BAI ; Qingda LI ; Yukuan LEI ; Lei ZHU ; Zhen CHANG ; Zhigang ZHAO ; Yunfei HUANG ; Mingzhe FENG ; Liang YAN ; Hua HUI ; Lingbo KONG ; Baorong HE
Chinese Journal of Trauma 2025;41(2):148-156
Objective:To compare the clinical efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 49 patients with fracture and dislocation of the lower cervical spine who were admitted to Honghui Hospital, Xi′an Jiaotong University School of Medicine from May 2021 to October 2022, including 38 males and 11 females, aged 29-61 years [(39.3±7.3)years]. Injury segments involved C 3 in 12 patients, C 4 in 11, C 5 in 8, C 6 in 9 and C 7 in 9. Twenty-one patients were treated with S8 navigation system (navigation group, 84 screws), and 28 with TINAVI orthopedic robot (robot group, 112 screws). The two groups were compared in terms of the total surgical duration, single screw placement time, total screw placement time, distance between the screw and the anterior cortex, incision length, intraoperative radiation dose, intraoperative blood loss and length of hospital stay. The height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and American Spinal Injury Association (ASIA) grade were assessed before surgery and at 3 days after surgery. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 3 days, 3 months after surgery and at the last follow-up were compared. The accuracy of screw placement, intraoperative invasion rate of adjacent facet joints and rate of postoperative complications (infection, screw loosening, etc.) were evaluated. Results:All the patients were followed up for 12-16 months [(13.6±1.9)months]. In the navigation group, the total surgical duration, distance from the screw to the anterior cortex and the intraoperative radiation dose were (236.2±30.6)minutes, (2.0±0.2)mm and (374.3±90.3)mGy respectively, which were significantly shorter or less than those in the robot group [(278.4±20.7)minutes, (10.6±2.9)mm and (448.4±77.9)mGy] ( P<0.01). The single screw placement time, total screw placement time, incision length and intraoperative blood loss were (3.5±0.4)minutes, (23.9±0.5)minutes, (9.1±2.4)cm and (422.2±30.4)ml respectively, which were significantly longer or more than those in the robot group [(2.6±0.2)minutes, (17.9±0.7)minutes, (6.6±2.6)cm and (360.3±56.3)ml] ( P<0.01). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). No significant differences were observed in the height of the intervertebral space, Cobb angle, sliding distance between the vertebral bodies and ASIA grade between the two groups ( P>0.05). At 3 days after surgery, the height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and ASIA grade in both groups were significantly improved when compared with those before surgery ( P<0.05 or 0.01). There were no significant differences in VAS, JOA scores or NDI between the two groups before surgery, at 3 days, 3 months after surgery and at the last follow-up ( P>0.05). The VAS, JOA scores and NDI in both groups were gradually improved at 3 days, 3 months and at the last follow-up after surgery when compared with those before surgery ( P<0.05). There was no significant difference in the accuracy of screw placement of levels 0 and 0+1 between the two groups ( P>0.05). No significant difference in the intraoperative invasion rate of adjacent facet joints between the two groups was found ( P>0.05). There were no serious complications such as infection or screw loosening after surgery in both groups. Conclusions:For lower cervical fracture and dislocation, although there are more advantages in total surgical duration, screw holding force and radiation control regarding the navigation system, and more outstanding performance in screw placement efficiency, incision length and intraoperative blood loss regarding the orthopedic robot, both of them can effectively rebuild the cervical structure, improve neurological function, relieve postoperative pain, improve screw placement accuracy and reduce facet joint injury and serious complications. Selection of the best auxiliary screw placement system should comprehensively consider patients′ conditions and the experience of the surgical team.
4.Clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy
Feng WU ; Yanan SHI ; Tian YAO ; Hao CHEN ; Yafei CHENG ; Shaoxiong BAI ; He HUANG ; Yuntong GUO
Chinese Journal of Digestive Surgery 2025;24(8):1061-1066
Objective:To investigate the clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 105 patients who underwent symmetrical three-port LSG at The First Hospital of Shanxi Medical University from October 2021 to October 2024 were collected. There were 57 males and 48 females, aged 27(range, 19-59)years. Of the 105 patients, 52 cases with continuous Bougie tube use during the surgery were divided into continuous group, while 53 cases with intermittent Bougie tube use were divided into intermittent group. Observation indicators: (1) surgical situations; (2) complications. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 105 patients underwent symmetrical three-port LSG. The operation time was (57±4)minutes versus (76±4)minutes for the continuous group and the intermittent group, volume of intraoperative blood loss was (26±6)mL versus (59±9)mL, time to first out-of-bed activities was (218±8)minutes versus (299±9)minutes, time to first anal exhaust was (19.6±2.9)hours versus (25.8±2.8)hours, visual analogue scale score for pain at 6 hours postoperatively was 2.3±1.0 versus 4.7±1.0, and duration of postoperative hospital stay was (1.5±0.6)days versus (3.1±0.9)days for the two groups, respectively. There were significant differences in the above indicators between the two groups( t=26.92, 22.31, 48.91, 11.15, 13.25, 10.21, P<0.05). (2) Complications. No severe postopera-tive complication occurred in any of the 105 patients. There were 26 cases and 38 cases with nausea and vomiting at 2 hours postoperatively, showing a significant difference between them ( χ2=5.19, P<0.05). Conclusion:Compared to intermittent Bougie tube use, continuous Bougie tube use during symmetrical three-port LSG can significantly shorten operation time and duration of postoperative hospital stay, reduce intraoperative bleeding and postoperative pain, accelerate recovery of patients, and lower the incidence of complications.
5.Clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy
Feng WU ; Yanan SHI ; Tian YAO ; Hao CHEN ; Yafei CHENG ; Shaoxiong BAI ; He HUANG ; Yuntong GUO
Chinese Journal of Digestive Surgery 2025;24(8):1061-1066
Objective:To investigate the clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 105 patients who underwent symmetrical three-port LSG at The First Hospital of Shanxi Medical University from October 2021 to October 2024 were collected. There were 57 males and 48 females, aged 27(range, 19-59)years. Of the 105 patients, 52 cases with continuous Bougie tube use during the surgery were divided into continuous group, while 53 cases with intermittent Bougie tube use were divided into intermittent group. Observation indicators: (1) surgical situations; (2) complications. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 105 patients underwent symmetrical three-port LSG. The operation time was (57±4)minutes versus (76±4)minutes for the continuous group and the intermittent group, volume of intraoperative blood loss was (26±6)mL versus (59±9)mL, time to first out-of-bed activities was (218±8)minutes versus (299±9)minutes, time to first anal exhaust was (19.6±2.9)hours versus (25.8±2.8)hours, visual analogue scale score for pain at 6 hours postoperatively was 2.3±1.0 versus 4.7±1.0, and duration of postoperative hospital stay was (1.5±0.6)days versus (3.1±0.9)days for the two groups, respectively. There were significant differences in the above indicators between the two groups( t=26.92, 22.31, 48.91, 11.15, 13.25, 10.21, P<0.05). (2) Complications. No severe postopera-tive complication occurred in any of the 105 patients. There were 26 cases and 38 cases with nausea and vomiting at 2 hours postoperatively, showing a significant difference between them ( χ2=5.19, P<0.05). Conclusion:Compared to intermittent Bougie tube use, continuous Bougie tube use during symmetrical three-port LSG can significantly shorten operation time and duration of postoperative hospital stay, reduce intraoperative bleeding and postoperative pain, accelerate recovery of patients, and lower the incidence of complications.
6.Ultrasound-guided needle knife release with different pathways for carpal tunnel syndrome: a randomized controlled trial.
Zhaobao LI ; Song HE ; Longyu XIE ; Hehuizi BAI ; Dejun CHENG ; Wenchao ZHANG ; Mingyong HUANG
Chinese Acupuncture & Moxibustion 2025;45(1):21-26
OBJECTIVE:
To evaluate the clinical efficacy of ultrasound-guided needle knife release with different pathways for carpal tunnel syndrome (CTS).
METHODS:
Sixty CTS patients were randomly divided into a transverse group and a longitudinal group, with 30 patients in each group. The transverse group received the needle knife release under ultrasound above and below the median nerve along the short axis, while the longitudinal group received the needle knife release under ultrasound above the median nerve along the long axis. The patients' visual analogue scale (VAS) scores, Levine scores, and median nerve cross-section area (CSA) were assessed before treatment, on the 7th, 14th, and 30th days after treatment. The median nerve conduction indexes (motor conduction: latency [Lat], amplitude[Amp], motor conduction velocity [MCV]; sensory conduction: Lat, Amp, sensory conduction velocity [SCV]) were evaluated before treatment and on the 30th day after treatment.
RESULTS:
Compared before treatment, the VAS scores, Levine scores, and median nerve CSA were reduced in both groups on the 7th, 14th, and 30th days after treatment (P<0.05); the transverse group showed lower VAS and Levine scores and smaller CSA than those in the longitudinal group (P<0.05). On the 30th day after treatment, motor and sensory Lat was reduced (P<0.05), motor and sensory Amp was increased (P<0.05), and MCV and SCV were faster (P<0.05) in both groups. The transverse group had shorter Lat, higher Amp, and faster MCV and SCV than those in the longitudinal group (P<0.05).
CONCLUSION
The ultrasound-guided needle knife release with transverse and longitudinal pathways could both effectively alleviate pain and improve median nerve conduction in CTS patients, with the transverse pathway showing superior efficacy to longitudinal pathway.
Humans
;
Carpal Tunnel Syndrome/therapy*
;
Female
;
Middle Aged
;
Male
;
Adult
;
Median Nerve/physiopathology*
;
Acupuncture Therapy/instrumentation*
;
Treatment Outcome
;
Neural Conduction
;
Aged
;
Ultrasonography
7.Clinical observation on jingjin needling combined with rehabilitation training in patients with post-stroke spastic paralysis.
Yuneng CAO ; Wei ZHANG ; Yaqin BAI ; Chengya HAO ; Zhenyan HE ; Aijun CHENG
Chinese Acupuncture & Moxibustion 2025;45(6):717-722
OBJECTIVE:
To compare the clinical efficacy of jingjin needling combined with rehabilitation training and conventional acupuncture combined with rehabilitation training for post-stroke spastic paralysis.
METHODS:
A total of 60 patients with post-stroke spastic paralysis were randomly divided into an observation group and a control group, 30 cases in each one. Both groups received conventional rehabilitation training. In the observation group, jingjin needling was applied at tendon blockage points of the shoulder, elbow, wrist, hip, knee, and ankle. In the control group, conventional acupuncture was applied at Jianyu (LI15), Quchi (LI11), Hegu (LI4), Biguan (ST31), Fengshi (GB31), Taichong (LR3), etc. on the affected side. Treatment was given once daily, 5 days a week for 4 weeks in both groups. The scores of clinical spasticity index (CSI), modified Ashworth scale, modified Barthel index (MBI), and Fugl-Meyer assessment scale (FMA) were evaluated before and after treatment, and the onset time was compared between the two groups.
RESULTS:
After treatment, the scores of CSI and modified Ashworth scale were decreased compared with those before treatment (P<0.001), while the scores of MBI and FMA were increased compared with those before treatment (P<0.001) in the two groups. After treatment, the scores of CSI and modified Ashworth scale in the observation group were lower than those in the control group (P<0.05), the MBI score in the observation group was higher than that in the control group (P<0.05). There was no statistically significant difference in FMA scores between the two groups (P>0.05). The onset time of the observation group was earlier than that in the control group (P<0.05).
CONCLUSION
Both jingjin needling combined with rehabilitation training and conventional acupuncture combined with rehabilitation training can effectively treat post-stroke spastic paralysis, jingjin needling combined with rehabilitation training exhibits better therapeutic effect and rapider onset.
Humans
;
Acupuncture Therapy
;
Male
;
Female
;
Middle Aged
;
Aged
;
Stroke/complications*
;
Adult
;
Acupuncture Points
;
Muscle Spasticity/etiology*
;
Treatment Outcome
;
Stroke Rehabilitation
;
Paralysis/therapy*
;
Combined Modality Therapy
8.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
;
Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
9.Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.
Cheng-Xian LI ; Xiao-He XIAO ; Xin-Yu LI ; Da-Ke XIAO ; Yin-Kang WANG ; Xian-Ling WANG ; Ping ZHANG ; Yu-Rong LI ; Ming NIU ; Zhao-Fang BAI
Chinese journal of integrative medicine 2025;31(2):142-152
OBJECTIVE:
To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma.
METHODS:
In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously.
RESULTS:
In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01).
CONCLUSIONS
Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity*
;
Animals
;
Humans
;
NAD(P)H Dehydrogenase (Quinone)/genetics*
;
HEK293 Cells
;
Kidney/pathology*
;
Cytochrome P-450 CYP1A2/genetics*
;
Mice, Inbred C57BL
;
DNA Adducts/drug effects*
;
Male
;
Kidney Diseases/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Mice
;
Prunus armeniaca
;
Plant Extracts
10.Identification of associated factors and construction of a predictive model for membranous nephropathy patients with IgM deposition
Lei HE ; Yunhui ZHANG ; Jingjing JIN ; Meijuan CHENG ; Shenglei ZHANG ; Yaling BAI ; Jinsheng XU
Chinese Journal of Nephrology 2025;41(7):489-497
Objective:To explore the associated factors for membranous nephropathy (MN) patients with IgM deposition, and to construct a prediction model.Methods:This study was a retrospective cohort study. Patients diagnosed with MN with IgM deposition by renal biopsy in the Fourth Hospital of Hebei Medical University from February 2017 to December 2023 were retrospectively included. Clinical and pathological data were collected. The study population was randomized into a training set and a validation set at a 7:3 ratio. The endpoint event was defined as the remission of MN, and the patients were divided into remission group and non-remission group to compare the clinical and pathological examination results. Least absolute shrinkage and selection operator regression analysis and Cox regression analysis were used to explore the associated factors of poor prognosis of MN patients with IgM deposition. Internal validation was conducted using the validation set data. The clinical efficacy of the predictive model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve and generating calibration curves. The total nomogram score for each patient was calculated based on the training set data, and the predictive performance was assessed by plotting the ROC curve. Patients were then stratified into low-risk and high-risk groups according to the optimal cut-off value derived from the ROC analysis of the total nomogram score. Kaplan-Meier survival analysis was performed to compare the remission rate between the two groups. Model performance was evaluated using the validation set.Results:A total of 200 MN patients with IgM deposition were included, and 49.0% of them achieved clinical remission. In the training set, statistically significant differences were observed in 24-hour urine protein quantification ( Z=-2.638, P=0.008), renal arteriolar wall thickening ( χ2=6.891, P=0.009), the proportion of patients receiving immunosuppressive therapy ( χ2=21.381, P<0.001), and the proportion of patients treated with corticosteroids combined with cyclophosphamide ( χ2=10.107, P=0.001). Through least absolute shrinkage and selection operator regression and Cox regression, 2 factors associated with clinical remission in MN patients with IgM deposition were simultaneously identified from 16 potential associated factors, including the use of immunosuppressants ( HR=3.823, 95% CI 2.055-7.113, P<0.001), and renal arteriolar wall thickening ( HR=0.428, 95% CI 0.221-0.831, P=0.012). Incorporating the clinical measurement of phospholipase A2 receptor (PLA2R) antibodies, a predictive model was established. The performance of the model was evaluated using the training dataset, yielding an area under the ROC curve of 0.731 (95% CI 0.648-0.814), with a sensitivity of 88.7% and a specificity of 55.1%. The optimal cut-off value was a total nomogram score of 41.7 points. The Kaplan-Meier survival analysis showed that the remission rate was significantly higher in the low-risk group than that of the high-risk group (Log-rank test, χ2=33.525, P<0.001). Model validation was performed using the validation dataset, which showed an AUC of 0.715 (95% CI 0.591-0.839), sensitivity of 70.4%, and specificity of 63.6%. Similarly, the Kaplan-Meier survival analysis demonstrated a significantly higher remission rate in the low-risk group than in the high-risk group (Log-rank test, χ2=8.467, P=0.004). Conclusion:A nomogram predictive model for remission of MN patients with IgM deposition, based on serum PLA2R antibody levels, the use of immunosuppressive therapy, and renal arteriolar wall thickening is developed. The model demonstrates a moderate clinical applicability.

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