1.Exploring on Mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos in Treatment of Acute Lung Injury Based on Serum Metabolomics
Wanshun CHANG ; Kang LI ; Zhaohua CHEN ; Yuqing HAN ; Yanwen CHEN ; Yanhui ZHU ; Zhenyu CHENG ; Haiying HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):117-125
ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos(FF) in the treatment of acute lung injury(ALI) by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week, and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide(LPS) solution by tracheal drip to establish an ALI model. After successful model establishment, the rats were randomly divided into the model group, the FF low-dose group(3.0 g·kg-1), the FF high-dose group(6.0 g·kg-1), and the dexamethasone group(5 mg·kg-1), with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution, and the blank group and the model group were gavaged with an equal amount of saline, treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin(HE) staining, wet/dry mass ratio(W/D) of the lung tissues, and protein concentration in rat bronchoalveolar lavage fluid(BALF). Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), combined with multivariate statistical analysis, the potential biomarkers of FF in treating ALI were screened by variable importance in the projection(VIP) value>1, P<0.05 from t-test, and log2fold change(FC)>1 or log2FC<-1. Kyoto Encyclopedia of Genes and Genomes(KEGG) database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate(S1P), phosphatidylinositol 3-kinase(PI3K), protein kinase B1(Akt1), and phosphorylated Akt1(p-Akt1) were examined by Western bolt. The expression levels of interleukin(IL)-6, IL-1β, and tumor necrosis factor(TNF)-α in BALF were detected by enzyme-linked immunosorbent assay(ELISA). ResultsCompared with the blank group, rats in the model group showed ALI pathological features such as alveolar lumen dilatation, interstitial hemorrhage and massive inflammatory cell infiltration, and the protein concentration in BALF and W/D of the lung tissues were significantly elevated(P<0.01). Compared with the model group, the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats, and the protein concentration in BALF and W/D were significantly decreased(P<0.05), and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways, including arginine biosynthesis, sphingomyelin metabolism, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, α-linolenic acid metabolism, niacin and nicotinamide metabolism, and retinol metabolism. The results of Western bolt and ELISA showed that, compared with the blank group, the model group exhibited significantly elevated expression levels of S1P, PI3K, Akt1 and p-Akt1 proteins in the lung tissues, as well as increased expression levels of IL-6, IL-1β and TNF-α in BALF(P<0.01). Compared with the model group, the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group(P<0.05, P<0.01). ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism, and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.
2.Study on the decision-making mechanism of the party branch of university affiliated hospital partici-pating in clinical business department
Ying ZHANG ; Shuyun WANG ; Junna CUI ; Zhaohua LIU ; Zhaoquan HUANG
Modern Hospital 2024;24(9):1343-1346,1349
As the key of colleges and universities and medical career,the affiliated hospital's clinical department is the core of its development.In the new era,strengthening the mechanism of party branch participating in the decision-making of clin-ical departments is an inevitable requirement for implementing the party's leadership and strengthening hospital management.The Party branch of the affiliated hospital of the university has the"dual"attribute,through the establishment of the"core group"of the party branch to participate in decision-making in the clinical business department,the establishment of an efficient decision-making platform,the construction mechanism of supporting rules of procedure and supervision measures to realize its function,the in-depth analysis of management challenges and the improvement of countermeasures,in order to create a new way and a new mechanism of the party branch decision-making,and promote the deep integration of party building and business.
3.Investigation of Mechanism of Qingqiao and Laoqiao on Acute Lung Injury Rats Based on Serum Metabolomics
Kang LI ; Tiantian LYU ; Rongqia CUI ; Shumin XIE ; Shujie GUO ; Wanshun CHANG ; Zhaohua CHEN ; Yanhui ZHU ; Mingsan MIAO ; Haiying HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):89-97
ObjectiveSerum metabolomics of acute lung injury(ALI) in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) to explore the similarities and differences in the mechanism of Qingqiao(harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color) and Laoqiao(harvested when the fruits of Forsythiae Fructus were ripe) in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week, 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide(LPS). After successfully constructing the ALI model, these rats was randomly divided into model group, Qingqiao group and Laoqiao group, with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg-1, while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin(HE) staining, wet-to-dry mass ratio(W/D) of lung tissues, and protein concentration in rat bronchoalveolar lavage fluid(BALF). The levels of interleukin(IL)-6, IL-1β and tumor necrosis factor(TNF)-α in BALF were quantified using enzyme-linked immunosorbent assay(ELISA). UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao, and serum metabolomics of rats in each group was analyzed, combined with multivariate statistical analysis with variable importance in the projection(VIP) value>1, P<0.05 from t-test, and fold change(FC)≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group, rats in the model group exhibited enlarged alveolar lumen, ruptured alveoli, interstitial hemorrhage, bronchial exudation of a large number of neutrophils and erythrocytes, and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues(P<0.01). In contrast, compared with the model group, rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs, and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased(P<0.01), the lung injury was significantly alleviated, but more obvious in the Qingqiao group. Compared with the blank group, the expression levels of IL-6, IL-1β and TNF-α in the BALF of the model group were significantly higher(P<0.01). Additionally, compared with the model group, the expression levels of IL-6, IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower(P<0.01). The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao, with 47 common components, 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats, 19 and 12 metabolites were called back by Qingqiao and Laoqiao, respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways, including linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, phenylalanine metabolism, ascorbate and aldarate metabolism, and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI, and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism, but the metabolic pathways affected by them are different.
4.Prospective clinical study on the influence of implant crown and bridge prostheses characteristics on peri-implant disease
Min TIAN ; Rui ZHAO ; Jin HUANG ; Zhaohua JI ; Ming FANG ; Yan DONG ; Li CHEN ; Lina NIU ; Jihua CHEN
Chinese Journal of Stomatology 2021;56(12):1197-1204
Objective:To investigate the influence of different characteristics of implant-supported fixed dental prostheses on the incidence of peri-implant disease.Methods:Prospective cohort was established for patients who received implant-supported fixed dental prostheses at the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University between June 2014 and September 2015. Several patient-related factors, implant prostheses factors, and oral hygiene maintenance factors were collected. The Log-rank test was used to compare the peri-implant disease rates of various factors, and the Cox proportional hazards model was used to conduct multivariate study on single factor significant factors to analyze the impact on the incidence of peri-implant disease.Results:A total of 214 subjects and 351 implants were included in the cohort, the follow-up period was (11.0±3.5) months. Finally, 43.0% (92/214) of patients and 37.3% (131/351) of implants developed peri-implant diseases. The incidence of peri-implant mucositis and peri-implantitis was 41.1% (88/214) and 4.2% (9/214) at the subject level,and 34.2% (120/351) and 3.1% (11/351) at the implant level. Among the factors associated with the implant prosthesis, single factor Log-rank analysis showed that prostheses retention methods, proximal contact of the prostheses, occlusion situation were statistical significance ( P<0.05). Multivariate analysis using Cox proportional hazards model showed that screw retention (hazard ratio=2.38, 95% CI: 1.42-3.99), proximal contact loss of the prostheses (hazard ratio=2.36, 95% CI: 1.31-4.27) were independent risk factors for peri-implant disease ( P<0.05). Conclusions:Factors such as prostheses retention mode and proximal contact characteristics have important influence on the health status of the implant.
5.Application of microvascular clip in treatment of vascular injuries——a report in research progress
Zhaohua HUANG ; Xiaohuan ZHAN ; Jile FU ; Junqing GAO
Chinese Journal of Microsurgery 2020;43(1):101-104
Objective:Microvascular clip plays important role in microsurgery. Therefore, the development of microvascular clips and research in clamp-related vascular injuries becomes a major topic. Based on clamp-related microvascular injuries, the study investigated in 4 aspects: injury assessment, vascular characteristics and blood vessel injury, vessel repair, and development of microvascular clamp. A prospects of the current researches is also given.
6.Application of Flow-through latissimus dorsi musculocutaneous flap to repair the wounds in children’s limb
Jile FU ; Huajie LUO ; Xiaohuan ZHAN ; Jiasheng ZHANG ; Xi WANG ; Zhaohua HUANG ; Xue LI ; Junqing GAO
Chinese Journal of Microsurgery 2020;43(3):261-265
Objective:To explore the method and clinical efficacy of Flow-through latissimus dorsi musculocutaneous flap to repair children’s limb wounds.Methods:From January, 2017 to September, 2019, the Flow-through latissimus dorsi myocutaneous flap was used to repair the limb wounds in 9 children, which were 3 cases of upper extremity wounds and 6 cases of lower extremity wounds. The patients were 5-12 years old, with an average age of 9.4 years. The wound debridement was performed in the first stage, and the wound was covered with VSD. The second operation was performed 5-8 days later. Flow-through free latissimus dorsi muscle flap was used to repair the wound, and 6 patients combined with skin grafting. During the operation, both ends of the recipient area artery were trimmed into a downward slant. The proximal end of the recipient area blood vessel was coincided with the subscapular artery, the distal end was coincided with the circumflex scapular artery, and the thoracodorsal vein and the recipient area vein were coincided. One patient had 2 thoracodorsal veins, and 8 patients had 1 thoracodorsal vein. After the operation, the patients were given anti-infection, anticoagulation and antispasmodic treatment. And regular follow-up.Results:In this group, 8 flaps survived completely, and 1 had partial epidermal necrosis, which healed under the scab. Skin grafting survives well. Nine patients were followed-up for 3 to 28 months, 7 of which were followed-up in the outpatient clinic, and 2 by WeChat. CDU showed smooth blood flow in all patients 1 month after operation, in addition of 3 after 1 year. The flap had good blood flow and soft texture. Flap plastic surgery was performed in 3 cases.Conclusion:Using Flow-through latissimus dorsi musculocutaneous flap to repair the wounds of the children’s limbs, the flap survived well after the operation, and the blood circulation of the main vessel in the affected area was smooth, which had no obvious effect on the blood supply to the distal limb of the affected area.
7. Two different methods of free iliac flap grafting in the repair of tibial defect
Piyu ZHOU ; Shaopu YANG ; Shangquan LI ; Qibo SU ; Yuanjun MA ; Zhenhua HUANG ; Linhu ZHANG ; Liang ZHAO ; Jiang HUANG ; Zhaohua WANG ; Bo LIU ; Qingsong ZHENG ; Qinchao ZHANG ; Yong ZHANG
Chinese Journal of Plastic Surgery 2019;35(12):1230-1233
Objcetive:
To explore the treatment of long segment defect of tibia by using tensor fascia lata combined with iliac flap or deep circumflex iliac pedicle iliac flap.
Methods:
From February 2012 to August 2017, The People′s Hospital of Zun Yi City Bo Zhou District treated 16 patients who had long segment defect of tibia.There were 11 males and 5 females, age from 22 to 58 years old, the average age was 42 years old. Iliac flap grafting with tensor fascia lata combined with iliac flap or deep circumflex iliac pedicle was used to treat the defect of long segment of tibia. There were 4 cases with simple tibial defect and 12 cases with skin defect. The longest tibial defect was 5-8 cm.
Results:
In this study, four patients used iliac flaps with deep circumflex iliac pedicle, the area of flaps ranged from 2.5 cm×5.0 cm to 5.0 cm×10.0 cm, while the area of iliac flaps ranged from 5.0 cm×2.5 cm to 8.0 cm×4.0 cm. Twelve patients used grafting with tensor fascia lata combined with iliac flap, the area of flaps ranged from 5.0 cm×12.0 cm to 12.0 cm×23.0 cm, while the area of iliac flaps ranged from 7.0 cm×2.0 cm to 8.0 cm×4.0 cm. All 16 cases of bone flap were survived, fracture healing, without surgical complications. The average follow-up period was 1.5 years, the flaps had good appearance in 10 cases and was slightly bloated in 6 cases; the ankle had normal motion in 14 cases and had poor dorsal extension in 2 cases. X-ray films showed that the bone flap repaired the bone defects and reached bone healing.
Conclusions
Vascularized tensor fascia lata combined with iliac flap or deep circumflex iliac pedicle iliac flap grafts increase local blood supply and accelerate the process of fracture healing.
8.Expression levels of serum osteopontin, adenosine kinase 1 and Dikkopf 1 in patients with lung cancer and their clinical significances
Shuqiang WU ; Hehe LIAO ; Jialin WANG ; Mingzhi REN ; Huiyun HUANG ; Zhaohua ZHAO
Cancer Research and Clinic 2019;31(3):149-153
Objective To observe the expression levels of serum osteopontin (OPN),adenosine kinase 1 (TK1) and secretory protein Dikkopf 1 (DKK1) in patients with lung cancer and their clinical significances.Methods Lung cancer patients treated in the First Affiliated Hospital of Xi'an Medical University from February 2017 to April 2018 were selected as the lung cancer group (60 cases),and 60 healthy adults who received physical examination in the same period were selected as the control group.The differences of serum OPN,TK1 and DKK1 levels between the lung cancer group and the control group and lung cancer patients with different characteristics were compared.Measurement data were compared by using t test.Results The levels of serum OPN,TK1 and DKK1 in lung cancer patients were (38.56±3.18) μg/L,(4.69±1.03) pmol/L and (3.76±0.89) ng/ml,respectively,which were higher than those in the control group [(15.98±2.06) μg/L,(1.01±0.22)pmol/L,(1.21±0.24) ng/ml;t =-46.162,-27.064,-21.428,all P < 0.01].The levels of serum OPN,TK1 and DKK1 in lung cancer patients of different ages and gender had no statistical differences (all P > 0.05).The levels of serum OPN,TK 1 and DKK1 in stage Ⅲ-Ⅳ lung cancer patients were (57.18 ±3.12) μg/L,(6.26±1.28) pmol/L and (4.98±1.03) ng/ml,respectively,which were higher than those in stage Ⅰ-Ⅱ lung cancer patients [(30.35±2.96) μg/L,(3.49±0.67) pmol/L,(3.01±0.96) ng/ml;t =-34.156,-10.690,-7.665,all P < 0.01].The levels of serum OPN,TK 1 and DKK1 in non-small cell lung cancer (NSCLC) patients were (55.13±5.02) μg/L,(5.96±1.11) pmol/L and (5.02±1.32) ng/ml,respectively,which were higher than those in small cell lung cancer (SCLC) patients [(29.68±3.16) μg/L,(3.13±0.98) pmol/L,(2.86±0.56) ng/ml;t =-22.353,-10.213,-7.688,all P < 0.01].Conclusion The levels of serum OPN,TK1 and DKK1 in patients with lung cancer are higher,which are related to the type and stage of lung cancer.
9.Establishment of rabbit subarachnoid hemorrhage model and the imaging findings of a little amount of subarachnoid hemorrhage in acute phase
Liang HUANG ; Peiling LI ; Zhaohua ZHAI ; Long ZHAO ; Xiangjun FANG
Journal of Practical Radiology 2017;33(5):777-780,787
Objective To explore the sensitivity of a little amount of subarachnoid hemorrhage (SAH) between CT and different MR sequences through animal experiment,to find a more sensitive way to diagnosis SAH.Methods 18 healthy adult white New Zealand rabbits were randomly divided into two experimental groups(group A and group B) and one control group(group C).Rabbit SAH model was established by injecting blood into the cisterna magna one time.All rabbits underwent CT and MR scan at 2 hours,48 hours after operation.The findings on CT and different MR sequences were observed and recorded.Results ①In experimental groups(group A and group B),MR FLAIR sequences in the diagnosis of a little amount of SAH was more sensitive than that on MR T1WI,T2WI and CT in acute phase.And the diagnosis sensitivity between MR FLAIR and CT was statistically significant(P<0.05).②Abnormal signs of SAH could not be found in group C.Conclusion ①Rabbit SAH model was established successfully which will be the foundation for the follow-up study of medical imaging.②MR FLAIR sequence is more sensitive to diagnose a little amount of SAH in acute phase,and may be used in the routine diagnosis of SAH in acute phase.
10.Clinical trial data management and quality metrics system.
Zhaohua CHEN ; Qin HUANG ; Yazhong DENG ; Yue ZHANG ; Yu XU ; Hao YU ; Zongfan LIU
Acta Pharmaceutica Sinica 2015;50(11):1374-9
Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.

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