1.Effects of Jiuwei Jianbu Drink on Oxidative Stress and Inflammatory Injury in Rats with Knee Osteoarthritis via the HMGB1/RAGE/PI3K/Akt Signaling Pathway
Yilong ZHAO ; Zhaojian ZHANG ; Guowei WANG
Journal of Medical Research 2025;54(8):48-55
Objective To investigate the effects of Jiuwei Jianbu Drink on oxidative stress and inflammatory injury in rats with knee osteoarthritis via the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation endproducts(RAGE)/phosphatidyli-nositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 60 rats were randomly divided into six groups according to the random number table method:blank control group,model group,positive drug group,and Jiuwei Jianbu Drink low-,medium-,and high-dose groups,with 10 rats in each group.Except for the blank control group,knee osteoarthritis models were estab-lished in the other groups,which were then subjected to corresponding treatments.Knee joint diameter and mechanical pain and thermal pain threshold changes were observed.Hematoxylin-eosin staining and safranin O/fast green staining were used to assess pathological changes in cartilage tissue.Oxidative stress markers and inflammatory factor levels in knee joint cartilage tissue of each group were meas-ured.Western blot was used to detect the expression of proteins related to the HMGB1/RAGE/PI3 K/Akt signaling pathway in knee joint tissues.Results Compared with the blank control group,the model group exhibited increased knee joint diameter and decreased mechan-ical pain and thermal pain threshold.Jiuwei Jianbu Drink at all doses groups and the positive control group significantly improved these in-dicators in a dose-dependent manner(P<0.05).Additionally,the Mankin score and Osteoarthritis Research Society International(OARSI)score in the model group were significantly higher than those in the blank control group,while Jiuwei Jianbu Drink intervention significantly reduced the OARSI score,with the best effect observed in the high-dose group(P<0.05).Compared with the blank con-trol group,the model group showed increased levels of nitric oxide(NO)and malondialdehyde(MDA),decreased levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and significantly elevated levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β).Compared with the model group,Jiuwei Jianbu Drink significantly inhibited oxidative stress and inflam-matory responses,especially at high doses(P<0.05).Moreover,the expression of HMGB1,RAGE,p-PI3K/PI3K,and p-Akt/Akt in the model group was higher than that in the blank control group,while Jiuwei Jianbu Drink intervention dose-dependently downregulat-ed the expression of these proteins(P<0.05).Conclusion Jiuwei Jianbu Drink alleviates oxidative stress and inflammatory injury in rats with knee osteoarthritis by inhibiting the HMGB1/RAGE/PI3K/Akt signaling pathway,thereby improving cartilage pathological chan-ges and demonstrating potential therapeutic value.
2.Smart bandage for chronic wound management
Mengyuan ZHANG ; Zhaojian WANG ; Jiuzuo HUANG ; Nanze YU ; Xiao LONG
Chinese Journal of Plastic Surgery 2025;41(10):1093-1097
The management of chronic wounds presents significant challenges, characterized by a low rate of healing and substantial impairment of patients’ quality of life, while also exerting a considerable strain on healthcare resources. Wound healing is a multifactorial and dynamic process, necessitating close monitoring of wound changes and timely, appropriate interventions. Smart bandage/dressing, an innovative approach born from interdisciplinary research, offers a new generation of wound care. It enables dynamic quantitative monitoring of wound conditions; facilitates transdermal drug release and physical mode therapeutics; and adjusts interventions in real time based on monitoring outcomes. In comparison to traditional wound dressings, smart bandages exhibit attributes such as real-time responsiveness, precision, and convenience. They not only simplify wound management but also enhance patient comfort and compliance, showcasing potential as a safe and effective treatment modality. Smart bandages hold promise for elevating the efficiency of managing chronic wounds, reducing morbidity rates, alleviating the burden of disease, and ultimately improving patients’ quality of life. This paper summarized the recent research progress of smart bandages and provided insights into novel wound care strategies.
3.Role of RhoA/ROCK2 signaling pathway in electroacupuncture preconditioning-induced reduction of perioperative neurocognitive disorders in aged rats
Chunxiao LIU ; Zhaojian LIU ; Jiajie ZHANG ; Yanan LI ; Lei SHI ; Qi ZHANG
Chinese Journal of Anesthesiology 2025;45(9):1142-1147
Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.
4.Role of RhoA/ROCK2 signaling pathway in electroacupuncture preconditioning-induced reduction of perioperative neurocognitive disorders in aged rats
Chunxiao LIU ; Zhaojian LIU ; Jiajie ZHANG ; Yanan LI ; Lei SHI ; Qi ZHANG
Chinese Journal of Anesthesiology 2025;45(9):1142-1147
Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.
5.Effects of Jiuwei Jianbu Drink on Oxidative Stress and Inflammatory Injury in Rats with Knee Osteoarthritis via the HMGB1/RAGE/PI3K/Akt Signaling Pathway
Yilong ZHAO ; Zhaojian ZHANG ; Guowei WANG
Journal of Medical Research 2025;54(8):48-55
Objective To investigate the effects of Jiuwei Jianbu Drink on oxidative stress and inflammatory injury in rats with knee osteoarthritis via the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation endproducts(RAGE)/phosphatidyli-nositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 60 rats were randomly divided into six groups according to the random number table method:blank control group,model group,positive drug group,and Jiuwei Jianbu Drink low-,medium-,and high-dose groups,with 10 rats in each group.Except for the blank control group,knee osteoarthritis models were estab-lished in the other groups,which were then subjected to corresponding treatments.Knee joint diameter and mechanical pain and thermal pain threshold changes were observed.Hematoxylin-eosin staining and safranin O/fast green staining were used to assess pathological changes in cartilage tissue.Oxidative stress markers and inflammatory factor levels in knee joint cartilage tissue of each group were meas-ured.Western blot was used to detect the expression of proteins related to the HMGB1/RAGE/PI3 K/Akt signaling pathway in knee joint tissues.Results Compared with the blank control group,the model group exhibited increased knee joint diameter and decreased mechan-ical pain and thermal pain threshold.Jiuwei Jianbu Drink at all doses groups and the positive control group significantly improved these in-dicators in a dose-dependent manner(P<0.05).Additionally,the Mankin score and Osteoarthritis Research Society International(OARSI)score in the model group were significantly higher than those in the blank control group,while Jiuwei Jianbu Drink intervention significantly reduced the OARSI score,with the best effect observed in the high-dose group(P<0.05).Compared with the blank con-trol group,the model group showed increased levels of nitric oxide(NO)and malondialdehyde(MDA),decreased levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and significantly elevated levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β).Compared with the model group,Jiuwei Jianbu Drink significantly inhibited oxidative stress and inflam-matory responses,especially at high doses(P<0.05).Moreover,the expression of HMGB1,RAGE,p-PI3K/PI3K,and p-Akt/Akt in the model group was higher than that in the blank control group,while Jiuwei Jianbu Drink intervention dose-dependently downregulat-ed the expression of these proteins(P<0.05).Conclusion Jiuwei Jianbu Drink alleviates oxidative stress and inflammatory injury in rats with knee osteoarthritis by inhibiting the HMGB1/RAGE/PI3K/Akt signaling pathway,thereby improving cartilage pathological chan-ges and demonstrating potential therapeutic value.
6.Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study
Qingrui WANG ; Shougen CAO ; Cheng MENG ; Xiaodong LIU ; Zequn LI ; Yulong TIAN ; Jianfei XU ; Yuqi SUN ; Gan LIU ; Xingqi ZHANG ; Zhuoyu JIA ; Hao ZHONG ; Hao YANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Surgery 2024;62(1):57-64
Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.
7.Smart bandage for chronic wound management
Mengyuan ZHANG ; Zhaojian WANG ; Jiuzuo HUANG ; Nanze YU ; Xiao LONG
Chinese Journal of Plastic Surgery 2024;40(10):1041-1045
The management of chronic wounds presents significant challenges, characterized by a low rate of healing and substantial impairment of patients’ quality of life, while also exerting a considerable strain on healthcare resources. Wound healing is a multifactorial and dynamic process, necessitating close monitoring of wound changes and timely, appropriate interventions. Smart bandage/dressing, an innovative approach born from interdisciplinary research, offers a new generation of wound care. It enables dynamic quantitative monitoring of wound conditions, facilitates transdermal drug release and physical mode therapeutics, and adjusts interventions in real time based on monitoring outcomes. In comparison to traditional wound dressings, smart bandages exhibit attributes such as real-time responsiveness, precision, and convenience. They not only simplify wound management but also enhance patient comfort and compliance, showcasing potential as a safe and effective new treatment modality. Smart bandages hold promise for elevating the efficiency of managing chronic wounds, reducing morbidity rates, alleviating the burden of disease, and ultimately improving patients’ quality of life. This paper summarized the recent research progress of smart bandages and provide insights into novel wound care strategies.
8.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
9.Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study
Qingrui WANG ; Shougen CAO ; Cheng MENG ; Xiaodong LIU ; Zequn LI ; Yulong TIAN ; Jianfei XU ; Yuqi SUN ; Gan LIU ; Xingqi ZHANG ; Zhuoyu JIA ; Hao ZHONG ; Hao YANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Surgery 2024;62(1):57-64
Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.
10.Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency
Juan ZHANG ; Chaowen YU ; Ming WANG ; Kexing WAN ; Jing YANG ; Zhaojian YUAN ; Zhihong LIAO ; Dongjuan WANG
Chinese Journal of Pediatrics 2024;62(1):66-70
Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

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