ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Objective: To investigate the characteristics of malignant tumor incidence and mortality in cancer registration areas of Zhejiang Province in 2021. Methods: Based on the 2021 cancer registration data from 22 national cancer registries in Zhejiang Province, the crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. Age standardized was performed using the age composition of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of malignant tumor in different genders, urban/rural areas and ages were described. The order of crude incidence and mortality of malignant tumor were analyzed. Results: In 2021, there were 116 639 new malignant tumor cases in Zhejiang Province. The crude, Chinese population standardized, and world population-standardized incidences were 530.93/100 000, 304.83/100 000, and 288.20/100 000, respectively. The cumulative incidence for 0 to 74 years was 31.92%. There were 40 475 death cases. The crude, Chinese population-standardized, and world population-standardized mortalities were 184.24/100 000, 79.40/100 000, and 78.97/100 000, respectively. The cumulative mortality for 0 to 74 years was 8.37%. The Chinese population-standardized incidence for males and females were 286.34/100 000 and 323.45/100 000, respectively, and the Chinese population-standardized mortality were 106.25/100 000 and 54.17/100 000, respectively. The Chinese population-standardized incidence for urban and rural were 316.85/100 000 and 285.11/100 000, respectively, and the Chinese population-standardized mortality were 75.59/100 000 and 85.48/100 000, respectively. The crude incidence and crude mortality of malignant tumor both increased with age, peaking in the groups aged 80-<80 and ≥85 years at 1 845.06/100 000 and 1 656.88/100 000, respectively. The top ten malignant tumors with the highest crude incidence were, in descending order: lung cancer, thyroid cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, liver cancer, cervical cancer, lymphoma, and brain tumors. These accounted for 80.34% of all new malignant tumor cases. The top ten malignant tumors with the highest crude mortality were, in descending order: lung cancer, liver cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, lymphoma, and gallbladder cancer. These accounted for 82.26% of all malignant tumor deaths. Conclusions In 2021, the cancer registration areas of Zhejiang Province were characterized by a relatively high malignant tumor incidence and a comparatively low mortality compared to national data. Males and the elderly emerged as key populations for targeted prevention and control. It is recommended to enhance screening, early diagnosis, and early treatment for lung cancer, thyroid cancer, prostate cancer, breast cancer, and gastric cancer malignancies.

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg^-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg^-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Objective     To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. Methods    Clinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results     Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P<0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion     In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.

Objective To observe the clinical efficacy and safety of esketamine injection combined with sufentanil injection for patient-controlled intravenous analgesia(PCIA)after fracture surgery in children.Methods Children scheduled for elective limb fracture incision and internal fixation were randomly divided into control group and treatment group.The control group was given 2 μg·kg-1 sufentanil for PCIA;the treatment group was given 1.0 mg·kg-1 esketamine combined with 1.5 μg·kg-1 sufentanil for PCIA.Background dose of 2 groups:2 mL·h-1,single dose of 2 mL each time,locking time of 15 min,total volume of 100 mL.The facial expression,leg movement,mobility,crying,consolability scale(FLACC)scores and Ramsay sedation scores,analgesic drug consumption and PCIA compression times within 48 h after operation,and adverse drug reactions were compared between the two groups at different time points after operation.Results Forty subjects enrolled in the treatment group,1 dropped out,and 39 were finally included in the statistical analysis;40 subjects enrolled in the control group,2 dropped out,and 38 were finally included in the statistical analysis.After treatment,the FLACC scores of treatment group at 2,4,6,12,24 and 48 h after operation were(4.75±0.93),(2.50±0.97),(1.75±0.93),(2.06±1.18),(1.13±0.62)and(0.50±0.63)points,which in control group were(6.13±1.13),(3.80±1.21),(2.87±0.64),(3.47±1.13),(1.87±0.92)and(1.27±0.80)points,and there were significant differences in the two groups(all P＜0.05).The Ramsay sedation scores of treatment and control groups at 2 hours after operation were(2.25±0.45)and(1.47±0.52)points;the number of effective PCIA compressions within 24 hours was 4.25±3.94 and 8.13±5.71;the amount of analgesic drugs used within 24 hours after surgery was(52.38±9.11)and(61.47±12.82)mL;the amount of analgesic drugs used within 48 hours after surgery was(88.81±14.31)and(94.60±5.93)mL,respectively;and the differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly dizziness,nausea and vomiting.The total incidences of adverse drug reactions in treatment and control groups were 53.85％and 84.21％with significant difference(P＜0.05).Conclusion Esketamine injection combined with sufentanil injection can reduce postoperative pain intensity,improve analgesic sedation effect and reduce the incidence of adverse reactions of analgesic pump after fracture surgery in children.

Objective To explore the effect of quercetin combined with iron death inhibitor Ferrostain-1 on oxalate-induced HK-2 cell injury.Methods HK-2 cells were randomly divided into control group(normal cultured cells),model group(0.5 mmol·L-1 calcium oxalate crystals),quercetin group(0.5 mmol·L-1 calcium oxalate crystals+100 μmol·L-1 quercetin),inhibitor group(0.5 mmol·L-1 calcium oxalate crystals+8 μmol·L-1 Ferrostain-1)and combination group(0.5 mmol·L-1calcium oxalate crystals+100 μmol·L-1quercetin+8 μmol·L-1 Ferrostain-1).Cell counting kit-8(CCK-8)assay was used to detect cell survival rate;Western blot was used to detect iron death related protein expression such as glutathione peroxidase 4(GPX4);flow cytometry and Tunel assay were used to detect cell apoptosis,and assay kit was used to detect cellular iron ions and antioxidant levels.Results The cell survival rates of control group,model group,quercetin group,inhibitor group and combination group were(100.00±2.55)％,(54.49±4.11)％,(64.26±6.30)％,(58.03±3.04)％and(79.37±4.29)％,respectively;GPX4 protein expression levels were 0.98±0.11,0.33±0.05,0.56±0.05,0.78±0.07 and 1.11±0.11,respectively;cell apoptosis rates were(4.15±0.28)％,(23.12±2.49)％,(17.28±1.07)％,(15.08±1.41)％and(8.95±0.75)％,respectively;Fe2+levels were(100.00±0.87)％,(162.55±14.70)％,(149.09±9.50)％,(144.95±11.12)％and(131.76±12.18)％,respectively;superoxide dismutase(SOD)levels were(58.67±3.46),(21.56±1.32),(33.60±2.03),(35.15±3.02)and(44.27±3.89)U·mL-1,respectively.The above indicators of the model group were compared with the control group,and the above indicators of the quercetin group,inhibitor group,and combination group were compared with the model group,the above indicators of the combination group were compared with the quercetin group,and inhibitor group,all they all showed statistical significance(all P＜0.05).Conclusion Iron death inhibitors can enhance the inhibitory effect of quercetin in vitro on oxalate-induced renal tubular epithelial cell injury.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners