1.Effect of Zhishi Daozhi Formula (枳实导滞方) on Intestinal Flora and TLR4/MyD88/NF-κB Signaling Pathway in Rats with Sepsis-Induced Gastrointestinal Dysfunction
Chenyu LIU ; Changhui LI ; Haoyang CHENG ; Zhiyang TIAN ; Yixuan LIU ; Jiuzhuo TIAN
Journal of Traditional Chinese Medicine 2026;67(18):2003-2010
ObjectiveTo investigate the effect and potential mechanism of Zhishi Daozhi Formula (枳实导滞方, ZDF) on inflammation in rats with sepsis-induced gastrointestinal dysfunction based on the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF‑κB) signaling pathway and intestinal flora. MethodsSixty SD rats were randomly divided into sham‑operation group, model group, ulinastatin group, and low‑, medium‑ and high‑dose ZDF groups, with 10 rats in each group. Except for the sham‑operation group, the rat model of sepsis‑induced gastrointestinal dysfunction was established by cecal ligation and puncture (CLP). Three days before modeling and 12 h after modeling, the low-, medium- and high-dose ZDF groups were intragastrically administered with ZDF solution at doses of 3.80, 7.60 and 15.20 g·kg⁻¹·d⁻¹, respectively. The ulinastatin group received intraperitoneal injection of ulinastatin at 100,000 U/kg, while the sham-operation and model groups were given normal saline at 1 ml/100 g by gavage. All interventions were performed once daily for 4 consecutive days. Tow hours after the last intervention, gastric emptying rate and small intestinal propulsion rate were detected. Gastrointestinal function indicators including D‑lactic acid (D‑LA) and intestinal fatty acid binding protein (i‑FABP), as well as inflammatory indicators including procalcitonin (PCT) and C‑reactive protein (CRP) were measured by ELISA 24 h after modeling. The counts of Escherichia coli, Bifidobacterium and Lactobacillus in the intestine were compared. The histopathological morphological changes of the rat intestinal mucosa were observed by HE staining. The protein and mRNA expressions of IκB kinase (Ikk), TLR4, MyD88 and NF‑κB in ileal tissues were detected by western blot and qRT‑PCR, respectively. ResultsCompared to the sham-operation group, the model group showed decreased gastric emptying rate and small intestinal propulsion rate, increased intestinal Escherichia coli count, elevated serum D‑LA, i‑FABP, PCT and CRP levels, increased protein and mRNA expressions of Ikk, TLR4, MyD88 and NF-κB in ileal tissue, decreased counts of Lactobacillus and Bifidobacterium (P<0.05), accompanied by obvious pathological injury of ileal mucosa. Compared to the model group, all medication groups exhibited significant improvements in the above mentioned indicators and alleviated intestinal mucosal injury (P<0.05). Compared to the ulinastatin group, except for D-LA in the medium-dose ZDF group, the differences in the above indicators between the low- and medium-dose ZDF groups were statistically significant (P<0.05), while the differences between the high-dose ZDF group and the ulinastatin group were not statistically significant (P>0.05). With increasing dosage, the gastric emptying rate, small intestinal propulsion rate, Lactobacillus and Bifidobacterium counts in the rats of all three ZDF groups increased, while the levels of serum D-LA, PCT, CRP, and i-FABP, the protein levels of Ikk, TLR4, MyD88, and NF-κB in intestinal tissue, and the Escherichia coli count decreased (P<0.05). ConclusionZDF can ameliorate intestinal mucosal injury, maintain intestinal flora balance and inhibit inflammatory response in rats with sepsis‑induced gastrointestinal dysfunction, with the high-dose group showing the best efficacy, which may be achieved by down‑regulating the TLR4/MyD88/NF-κB signaling pathway.
2.Application,research hotspots,and shortcomings of degradable zinc-based alloys in bone defect repair and reconstruction
Haoyang LIU ; Qiang XIE ; Mengran SHEN ; Yansong REN ; Jinhui MA ; Bailiang WANG ; Debo YUE ; Weiguo WANG
Chinese Journal of Tissue Engineering Research 2025;29(4):839-845
BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.
3.The diagnostic value of spectral CT calcium suppression technique in new traumatic rib fractures
Journal of Practical Radiology 2025;41(4):637-641
Objective To explore the feasibility and accuracy of spectral CT calcium suppression technique in the diagnosis of new traumatic rib fractures.Methods A total of 30 patients with a clear history of trauma and clinical diagnosis of rib fracture or suspected traumatic fracture were retrospectively selected.Rib spectral CT and MRI plain scan were performed within 24 h.All ribs were divided into 24 regions(the left and right ribs were divided into 12 regions respectively).Two physicians independently analyzed whether the ribs in each region had cortical discontinuity and used the spectral CT calcium suppression color image to evaluate whether the ribs had bone marrow edema.Bone marrow edema accompanied by cortical discontinuity was diagnosed as a new rib fracture,otherwise it was not a new rib fracture.Kappa test was used to analyze the consistency of the diagnosis results of the two physicians.χ2 test was used to compare the fracture type and bone marrow edema between spectral CT and MRI images.The CT values of all regions were measured with the MRI results as the reference standard,and the independent sample t test was used to analyze whether it was statistically significant.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of spectral CT calcium suppression technique for rib fractures.Results The accuracy of spectral CT calcium suppression technique in the diagnosis of bone marrow edema of rib fracture was 96.9%.The CT value of bone marrow edema region[(7.6±23.8)HU]was significantly higher than that of normal rib region[(-54.4±18.4)HU](P<0.000 1).The area under the curve(AUC)of spectral CT calcium suppression technique in the diagnosis of rib bone marrow edema was 0.989,and the cutoff value was-22.8.Conclusion Spectral CT calcium suppression technique has high sensitivity to new traumatic rib fractures,and can intuitively and quantitatively analyze bone marrow edema through pseudo-color images,providing a reference for clinical diagnosis of new rib fractures.
4.Establishment and investigation of the biological behavior of gemcitabine-resistant pancreatic cancer cell line
Haoyang ZHU ; Jiawei TIAN ; Shenao QU ; Shiran TAO ; Yirong AN ; Lu LU ; Chang LIU ; Yi LYU ; Nana ZHANG
Chinese Journal of Hepatobiliary Surgery 2025;31(1):59-65
Objective:To construct the gemcitabine resistant cell lines of human pancreatic cancer cell line (PANC1) and mouse pancreatic cancer cell line (PANC02), and to investigate their biological behavior changes.Methods:Gemcitabine-resistant cell lines PANC1-GR of human pancreatic cancer and PANC02-GR of mouse pancreatic cancer were induced by concentration gradient increment method. Cell count assay (CCK-8), flow cytometry, cell scratch assay and Transwell assay were used to detect the drug resistance, proliferation, cell cycle, migration and invasion of the four groups of cell lines. The drug-resistant cells were also compared with the parent cells.Results:The resistance indices of PANC1-GR and PANC02-GR were 153.3 and 185.4, respectively. The results of CCK-8 showed that with the increase of gemcitabine concentration, the proliferation of resistant cells changed significantly compared with parental cells, the population doubling time of PANC1-GR was significantly shorter than that of PANC1 (1.5±0.1) d vs (2.4±0.2) d ( t=8.00, P<0.001). The proportion of cells in S and G2/M phase increased, and the proportion of cells in G0/G1 phase decreased. The cell scratch and Transwell experiments indicated that the 24h mobility of PANC1-GR and PANC02-GR was higher than that of parent cells (47.6±2.4)% vs (28.7±6.3)% and (53.6±3.2)% vs (30.1±1.4)%, the number of individual field (200 times magnification) penetrating membrane cells was also higher than that of parent cells (269.7±30.9) vs (62.7±10.1) and (172.0±30.8) vs (36.3±4.9), with statistical significance (all P<0.05). Conclusion:Concentration gradient increment method can successfully establish gemcitabine-resistant pancreatic cancer cell lines, which have stronger proliferation, migration and invasiveness, and can be used to study the mechanism of drug resistance in pancreatic cancer.
5.Performance evaluation of VA/HA/β-TCP scaffold and its therapeutic effects on infectious bone defects of mice
Ying LIU ; Hua WEN ; Haoyang DING ; Jiliang WANG ; Jun ZHAO
Chongqing Medicine 2025;54(10):2289-2295,2301
Objective To evaluate the drug-loading performance,biocompatibility,bone tissue compati-bility,and therapeutic efficacy of vancomycin(VA)-loaded hydroxyapatite(HA)/β-tricalcium phosphate(β-TCP)scaffolds in treating infectious bone defects in mice.Methods HA/β-TCP scaffolds were fabricated by using 3D printing technology,and VA was loaded onto the scaffolds via freeze-drying to create the composite VA/HA/β-TCP scaffolds.The scaffolds were observed by using scanning electron microscopy(SEM),and their encapsulation efficiency,drug-loading capacity,and release kinetics were assessed.An in vitro co-culture system was established with mouse embryonic osteoblasts(MC3T3-E1)and the scaffolds,The cells were di-vided into the control group(HA/β-TCP scaffolds)and the VA/HA/β-TCP group.Cell viability was assessed by using the methyl thiazolyl tetrazolium(MTT)assay,and osteocalcin(OCN)expression levels were meas-ured by ELISA at 7,12,and 14 days of co-culture.Antibacterial activity was evaluated through adhesion ex-periments.A mouse cranial defect model was constructed and implanted with the scaffolds for 4 weeks.Hema-toxylin and eosin(HE)staining was performed to observe material degradation and bone formation in the sur-rounding tissues.Results The VA/HA/β TCP scaffolds exhibited uniform pore size distribution and excel-lent drug-loading performance,with an encapsulation efficiency of 70.32%and an actual drug-loading rate of 30.53%,effectively loading VA.The scaffolds sustained VA release over 36 hours.Compared to the control group,MC3T3-E1 cell viability on the VA/HA/β-TCP scaffolds was significantly inhibited at 7 and 12 days of co-culture(P<0.01),but no significant difference in proliferation activity was observed between the two groups after 14 days(P>0.05).No significant differences in OCN expression levels were found in MC3T3-E1 cells on the VA/HA/β-TCP scaffolds compared to the control group at any time point(P>0.05).The VA/HA/β-TCP scaffolds demonstrated strong antibacterial properties,with significantly reduced numbers of Escherichia coli in the co-cultured bacterial solution and on the scaffold surface compared to the control group(P<0.001).Compared with the control group,the VA/HA/β-TCP group demonstrated significantly reduced cranial hemorrhage and inflammatory infiltration,alongside a marked increase in new bone tissue.Conclusion The VA/HA/β-TCP scaffolds exhibit excellent drug-loading performance,controlled drug re-lease,biocompatibility,antibacterial activity,and bone tissue compatibility,offering a novel approach for trea-ting bone infections.
6.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
7.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
8.Effects and Mechanism of Cyclocaryae Paliuri Folium in Sodium Palmitate-Induced Lipid Deposition in HepG2 Cells
Yixuan LIU ; Haoyang WU ; Jingjing YANG ; Yuzhe CAI ; Zheng LUO ; Dingxiang LI ; Yihui DENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):72-78
Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.
9.Research progresses in gene therapy for hepatolenticular degeneration
Gui CHEN ; Haoyang ZHENG ; Fang LIU ; Jing YUAN ; Yuanhong XU ; Weisheng CHENG
Chinese Journal of Hepatology 2025;33(1):97-102
Hepatolenticular degeneration, also known as Wilson's disease, is a type of autosomal recessive genetic disorder of copper metabolism. The causative gene, ATP7B, is located on the long arm of chromosome 13 and encodes a P-type ATPase that is involved in copper transport. Pathogenic mutations in the ATP7B gene sequence lead to the diminished or lost function of the ATP7B protein, resulting in pathological copper deposition in organs such as the liver, brain, kidneys, and cornea. Currently, the treatment of Wilson's disease primarily involves oral medications to promote copper excretion or reduce copper absorption so as to alleviate the state of illness. However, pharmacological treatment has objective limitations, including the need for lifelong therapy and varying degrees of adverse drug reactions in some patients. Gene therapy can fully correct the genetic defect, restore ATP7B protein function, achieve a curative effect, and improve the patient's quality of life.
10.Preliminary Discussion on the Treatment of Hidden Penis with Brisson Technique Combined with Precise Measurement Scheme
Bin YANG ; Caixia LIU ; Na GUO ; Haoyang GAO ; Yi WANG ; Nan LI ; Haitao CHEN ; Yingchao LI
Journal of Clinical Surgery 2025;33(5):470-473
Objective To explore the clinical effect of using the Brisson technique combined with a precise measurement scheme in the treatment of hidden penis.Methods The clinical data of 120 children with hidden penis treated in our hospital from January 2021 to June 2024 were retrospectively analyzed.The enrolled children were randomly divided into the study group(n=60)and the control group(n=60).The study group was treated with the Brisson technique combined with a precise measurement scheme,and the cutting of the penile skin was designed according to the data.The control group was treated with the traditional Devine technique.The surgical effects,penile lengths before and after surgery,and the incidence of postoperative complications of the children in the two groups were compared and analyzed.Results The effective rate of the study group reached 100%,which was significantly higher than that of the control group(93%,P<0.05).Six months after surgery,the penile length of the children in the study group was longer than that in the control group,and the difference was statistically significant(P<0.05).The incidence of surgical complications in the study group was 5%,which was significantly lower than that in the control group(17%,P<0.05).Conclusion Using the Brisson technique combined with a precise measurement scheme to treat hidden penis has a good effect,a high effective rate,and a low incidence of complications.

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