1.Effect of Quercetin on Cuproptosis in Rheumatoid Arthritis Rats and Its Mechanism via SLC31A1/FDX1 Pathway
Haoruo YANG ; Qiuai KOU ; Junhua REN ; Guo YUAN ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):121-130
ObjectiveTo observe the influence and therapeutic effect of quercetin on cuproptosis in rheumatoid arthritis rats and to explore its possible mechanism based on the solute carrier family 31 member 1 (SLC31A1)/ferredoxin 1 (FDX1) pathway. MethodsSixty male SD rats were divided into six groups: A control group, a model group, high- and low-dose quercetin groups (150 and 50 mg·kg-1), a cuproptosis inhibitor (tetrathiomolybdate, TTM) group (10 mg·kg-1), and a methotrexate group (2 mg·kg-1), 10 rats in each group. Except for the control group, the model of rheumatoid arthritis (CIA) rats was established by type Ⅱ collagen induction method. After successful modeling, each drug group was intervened according to the corresponding dose of drugs, and the control group and the model group were given the same amount of normal saline by gavage, once a day, which lasted for 4 weeks. The swelling degree of rats' feet was observed, and the clinical arthritis scores were determined. The levels of serum rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), and ceruloplasmin (Cp) were detected by enzyme-linked immunosorbent assay (ELISA). The content of copper ion (Cu), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in joint tissue was detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of joint tissue. The levels of reactive oxygen species (ROS) and dihydrolipoic acid transacetylase (DLAT) were detected by immunofluorescence (IF). The protein and mRNA expression of SLC31A1, FDX1, lipoic acid synthase (LIAS), heat shock protein 70 (HSP70), pyruvate dehydrogenase E1 subunit β (PDHB), and copper transporting P-type ATPase β (ATP7B) was detected by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared to the control group, the model group exhibited joint swelling and deformity, significantly increased clinical arthritis scores, obvious bone destruction, synovial hyperplasia, and inflammatory cell infiltration in joint tissue. In addition, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp showed significant elevation, while the level of IL-10 was significantly reduced. The levels of Cu, MDA, ROS, and DLAT in joint tissue were markedly increased, whereas SOD and GSH content was significantly decreased. The protein and mRNA expression of SLC31A1 and HSP70 was significantly up-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was significantly down-regulated (P<0.01). Compared to the model group, each treatment group exhibited varying degrees of improvement in joint swelling and deformation as well as clinical arthritis scores in rats. Additionally, there was a reduction in joint bone destruction, inflammatory cell infiltration, and synovial hyperplasia in rats. Furthermore, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp significantly decreased, while the level of IL-10 increased significantly. In joint tissue, the levels of Cu, MDA, ROS, and DLAT showed significant decreases, while SOD and GSH content exhibited significant increases. The protein and mRNA expression of SLC31A1 and HSP70 was down-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was up-regulated (P<0.05). ConclusionQuercetin effectively reduces synovial hyperplasia and inflammatory infiltration in rats with rheumatoid arthritis, thereby alleviating pathological damage to joint tissue. This effect may be attributed to the blockade of the SLC31A1/FDX1 signaling pathway activation and inhibition of excessive cuproptosis.
2.Guideline for the workflow of clinical comprehensive evaluation of drugs
Zhengxiang LI ; Rong DUAN ; Luwen SHI ; Jinhui TIAN ; Xiaocong ZUO ; Yu ZHANG ; Lingli ZHANG ; Junhua ZHANG ; Hualin ZHENG ; Rongsheng ZHAO ; Wudong GUO ; Liyan MIAO ; Suodi ZHAI
China Pharmacy 2025;36(19):2353-2365
OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs, and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization (WHO), strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States, and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions; research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center, and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions, including topic selection, evaluation implementation, evidence evaluation, and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs, which can effectively guide the high-quality and high-efficient development of this work, enhance the standardized output and transformation application value of evaluation evidence, and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.
3.Gut microbiome and tumor immunotherapy
Ciliang GUO ; Chunping JIANG ; Junhua WU
Journal of International Oncology 2023;50(7):432-436
Neoplasms immunotherapy has made a major breakthrough in the clinical practice of refractory tumor. However, there are still individual differences in treatment results and drug resistance in clinical application. Gastrointestinal microbiome is gradually recognized as an immunoregulatory factor in recent years, and more and more studies have focused on its influences on the efficacy of tumor immunotherapy. Targeting gastrointestinal microbiota to improve the response of tumor patients to immunotherapy has potential clinical application value.
4.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
5.Risk factors for severe chest trauma complicated by acute respiratory distress syndrome
Junhua GUO ; Zhiming SONG ; Jianming CHEN ; Songlin CHEN ; Yunfeng YI
Chinese Journal of Trauma 2022;38(12):1089-1094
Objective:To investigate the risk factors of severe chest trauma complicated by acute respiratory distress syndrome (ARDS).Methods:A case control study was conducted to analyze the clinical data of 120 patients with severe chest trauma admitted to 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2018 to December 2020. There were 75 males and 45 females; aged 21-72 years [(42.2±4.8)years]. The causes of injury were traffic injury in 57 patients, crush injury in 21, fall injury in 21, smash injury in 11 and others in 10. There were 34 patients accompanied by fracture of the limb, spine and pelvis, 23 by abdominal organ injury and 8 by head trauma, with the exception of simple thoracic trauma in 55 patients. The patients were divided into ARDS group ( n=25) and non-ARDS group ( n=95) according to the condition of concurrent ARDS. The two groups were compared regarding the gender, age, causes of injury, respiratory rate, lung contusion, lung infection, flail chest, chest abbreviated injury scale (AIS), hemothorax, blood pressure, partial arterial oxygen pressure (PaO 2), initial central venous pressure (CVP) on admission, combined fracture of the limb, spine and pelvis, combined head injury and combined abdominal organ injury. The correlation between the above indexes and ARDS after severe chest trauma was analyzed by univariate analysis. Multivariate Logistic regression analysis was used to determine the independent risk factors for ARDS after severe chest trauma. Results:Univariate analysis showed a positive correlation of ARDS with age, respiratory rate, lung contusion, lung infection, flail chest, chest AIS, hemothorax, blood pressure, PaO 2, initial CVP on admission, combined fracture of the limb, spine and pelvis and combined abdominal organ injury ( P<0.05 or 0.01), but not with gender, causes of injury or combined head injury (all P>0.05). Multivariate Logistic regression analysis revealed that age ≥60 years ( OR=2.45, 95% CI 1.81-7.50, P<0.01), dyspnea (respiratory rate ≥28 times/minute or <10 times/minute) ( OR=9.55, 95% CI 2.26-9.38, P<0.01), lung contusion ( OR=6.78, 95% CI 1.84-6.96, P<0.01), lung infection ( OR=27.71, 95% CI 11.97-64.14, P<0.01), flail chest ( OR=8.97, 95% CI 2.29-14.97, P<0.01), chest AIS score ( OR=5.77, 95% CI 2.85-9.20, P<0.01), above medium amount of hemothorax ( OR=6.84, 95% CI 1.69-13.39, P<0.01), blood pressure <90 mmHg ( OR=7.93, 95% CI 1.64-11.84, P<0.01), PaO 2<60 mmHg ( OR=6.39, 95% CI 1.06-9.47, P<0.01) and absent initial CVP on admission ( OR=4.56, 95% CI 1.86-8.44, P<0.01) were significantly correlated with ARDS. Conclusion:Age ≥60 years, dyspnea (respiratory rate ≥28 times/minute or <10 times/minute), lung contusion, lung infection, flail chest, chest AIS, above medium l amount of hemothorax, blood pressure <90 mmHg, PaO 2<60 mmHg and absent initial CVP on admission are independent risk factors for ARDS in patients with severe chest trauma.
6.Risk assessment of nosocomial infection in children's specialist hospitals based on semi-quantitative assessment
Jie GAO ; Guangjun YU ; Jiangjiang XU ; Junhua GUO ; Lili SONG
Shanghai Journal of Preventive Medicine 2022;34(10):981-987
ObjectiveTo identify high-risk factors and high-risk process of nosocomial infection, and then take targeted prevention and control measures to improve nosocomial infection management. MethodsWe identified and determined the risk factors associated with nosocomial infection by using an expert brainstorming method, and then conducted risk assessment of the factors in the outcomes and process by using a semi-quantitative method. ResultsA total of 31 experts participated in the risk factor assessment. Risk assessment scores showed that nosocomial infection due to multi-drug resistant bacteria was the highest risk in the outcomes of nosocomial infection. Lack of isolation for airborne/droplet transmission, needle/sharp instrument injury, inadequate identification of infection risk and response measures in construction engineering, and insufficient implementation of infection control system were extremely high risk factors in the process of nosocomial infection. ConclusionPrevention and control should be strengthened on multi-drug resistant bacteria and catheter-related infections. The role of multidisciplinary team (MDT) in the prevention and control of nosocomial infection should be enhanced in medical practice. Risk assessment may facilitate the resource allocation and improve hand hygiene behavior.
7.Efficacy comparison of standardized incision and conventional incision for reduction and internal fixation of multiple rib fracture
Zhiming SONG ; Jianming CHEN ; Jing ZHONG ; Junhua GUO ; Xiaoping YU ; Songlin CHEN ; Weibin CAI ; Yuzhen ZHENG ; Yunfeng YI
Chinese Journal of Trauma 2022;38(11):977-984
Objective:To compare the efficacy of standardized incision and conventional incision for reduction and internal fixation of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 192 patients with multiple rib fracture treated in 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2020 to January 2022. There were 101 males and 91 females; aged 32-94 years [(51.5±16.6)years]. The patients underwent open reduction and internal fixation with nickel-titanium shape memory alloy embracer via standard incision such as anterior axillary longitudinal incision (standard incision group, n=96) or conventional incision such as posterolateral incision (conventional incision group, n=96). The incision length, operation time, intraoperative blood loss, number of fixed fractures, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time and length of hospital stay were compared in the two groups. The visual analogue scale (VAS) was used to evaluate pain at 1 month after operation. Postoperative complications were recorded. Results:All patients were followed up for 1-16 months [4.0(3.0, 10.5)months]. The operation time, intraoperative blood loss, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time, length of hospital stay and VAS at postoperative 1 month in standard incision group [(12.1±1.6)cm, (51.4±13.0)minutes, (191.5±16.8)ml, (2.8±0.6)days, (568.9±109.0)ml, (4.1±0.7)days, (11.4±1.7)days, (2.5±0.7)points] were better than those in conventional incision group [(13.7±1.9)cm, (62.0±8.8)minutes, (248.9±65.4)ml, (4.8±1.1)days, (655.9±121.9)ml, (5.2±0.9)days, (15.3± 1.7)days, (3.5±0.7)points] ( P<0.05 or 0.01). There was no statistical difference in the number of fixed fractures between standard incision group and conventional incision group (5.1±0.8 vs. 5.4±0.9) ( P>0.05). In standard incision group, there were 3 patients with poor wound healing, 5 with pulmonary infection, 3 with atelectasis and 3 with small pleural effusion. In conventional incision group, there were 11 patients with poor wound healing, 9 with pulmonary infection, 7 with atelectasis and 7 with small pleural effusion. The incidence of postoperative complications was 14.6% (14/96) in standard incision group and 35.4% (34/96) in conventional incision group ( P<0.01). Conclusion:For multiple rib fracture, standard incision is superior to conventional incision reduction in shortening the incision length, operation time, indwelling time of drainage tube, postoperative spontaneous ambulation time and length of hospital stay, reducing the intraoperative blood loss and postoperative thoracic drainage volume, alleviating the pain and reducing the postoperative complications.
8.Efficacy comparison of extracorporeal membrane oxygenation and ventilation therapy in the treatment of severe blast lung injury
Jianming CHEN ; Jing ZHONG ; Zhiming SONG ; Songlin CHEN ; Junhua GUO ; Xiaoping YU ; Weibin CAI ; Yan DOU ; Yunfeng YI
Chinese Journal of Trauma 2022;38(11):992-998
Objective:To compare the clinical efficacy of extracorporeal membrane oxygenation (ECMO) and ventilation therapy in the treatment of severe blast lung injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 37 patients with severe blast lung injury admitted to 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2000 to December 2021, including 23 males and 14 females; aged 26-50 years [(36.3±11.1)years]. The chest abbreviated injury score (AIS) was 3-5 points. In all, 16 patients were treated with ECMO from January 2017 to December 2021 (ECMO group) and 21 with ventilator from January 2000 to December 2016 (ventilator group). Blood gas analysis indexes [arterial pH, partial pressure of carbon dioxide (PaCO 2), partial pressure of oxygen (PaO 2), blood lactate (Lac)] and hemodynamics indexes [central venous pressure (CVP), cardiac output index (CI), pulmonary arterial systolic pressure (PASP), pulmonary capillary wedge pressure (PAWP)] were compared in the two groups at 30 minutes before treatment and at 2, 4, 6 hours after treatment. The mechanical ventilation time, ICU length of stay, acute physiology and chronic health evaluation II (APACHE II) score and mortality were measured at 7 days after treatment. Results:All patients were followed up for 24-48 months [(33.6±8.2)months]. The blood gas analysis and hemodynamic indexes were significantly improved in the two groups at 2, 4, 6 hours after treatment when compared with those at 30 minutes before treatment (all P<0.05), and the improvements were still statistically significant in ECMO group at 4, 6 hours after treatment when compared with those at 2 hours after treatment (all P<0.05), while not in ventilator group (all P>0.05). There was no significant difference in blood gas analysis indexes or hemodynamic indexes between the two groups at 30 minutes before treatment (all P>0.05). After treatment for 2, 4, 6 hours, blood gas analysis indexes and hemodynamic indexes in ECMO group were statistically different from those in ventilator group (all P<0.05). After treatment for 7 days, the mechanical ventilation time, ICU length of stay, APACHE II score and mortality were (3.2±1.2)days, (5.4±1.3)days, (14.1±3.3)points and 12.5% (2/16) in ECMO group, significantly different from (5.1±1.6)days, (7.6±1.6)days, (10.2±2.6)days and 28.6% (6/21) in ventilator group (all P<0.05). Conclusion:For severe blast lung injury, ECMO can attain rapid and continuous improvement of refractory hypoxemia and dyspnea, shorten the duration of mechanical ventilation and ICU length of stay and reduce the mortality rate when compared with ventilator therapy.
9.Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia Pacific experience.
Ling ZHANG ; Matthew COVE ; Binh G NGUYEN ; Nuttha LUMLERTGUL ; Kartik GANESH ; Alfred CHAN ; Giang T H BUI ; Chunwen GUO ; Junhua LI ; Songqiao LIU ; Mian PENG ; Kit W FOONG ; Jian ZHANG ; Minmin WANG ; Jacques GOLDSTEIN ; Kai HARENSKI
Chinese Medical Journal 2021;134(18):2258-2260
10.Expression and significance of chemokine CXCL12 and receptor CXCR4 in adenomyosis
Sha WANG ; Hua DUAN ; Bohan LI ; Yiyi WANG ; Junhua HUANG ; Zhengchen GUO
Chinese Journal of Obstetrics and Gynecology 2020;55(11):754-759
Objective:To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis.Methods:Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR.Results:(1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated ( r=0.478, 0.542, all P<0.05). Conclusions:The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

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