OBJECTIVES: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method. Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction. CONCLUSIONS Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Myocardial Infarction/complications* ; Transforming Growth Factor beta1/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Heart Failure/pathology* ; Myocardium/metabolism* ; Fibrosis ; Amino Acid Oxidoreductases/metabolism* ; Interleukin-11/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Matrix Metalloproteinase 9/metabolism*

Objective:To observe the clinical effect of initiating continuous blood purification (CBP) treatment at different times for patients with severe acute pancreatitis (SAP), and to explore the optimal timing for starting CBP treatment for SAP, so as to provide evidence for clinicians to start CBP treatment.Methods:A retrospective cohort study was used to select patients with SAP who received CBP treatment in People's Hospital of Hunan Province from January 2020 to December 2023. According to the timing of CBP initiation, the patients were divided into early initiation group (diagnosis of SAP to the first CBP treatment time < 24 hours) and late initiation group (diagnosis of SAP to the first CBP treatment time of 24-48 hours). The general data, acute physiology and chronic health evaluationⅡ(APACHEⅡ), bedside index for severity in acute pancreatitis (BISAP) score and laboratory indicators, local complications and systemic complications, intensive care unit (ICU) treatment time, hospital stay, treatment cost, and clinical outcome of the two groups were collected and compared.Results:A total of 130 patients with SAP who received CBP treatment were enrolled, including 90 patients in the early initiation group and 40 patients in the late initiation group. Before treatment, there were no significant differences in gender, age, APACHEⅡscore, BISAP score, etiology and laboratory examination indexes between the early initiation group and late initiation group. At 48, 72, 96 hours after treatment, the blood calcium level of the two groups was significantly higher than that before treatment, and the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic acid, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), APACHEⅡscore and BISAP score were significantly lower than those before treatment. The WBC level, APACHEⅡscore and BISAP score of the late initiation group were significantly lower than those of the early initiation group at 72 hours and 96 hours after treatment [WBC (×10 9/L): 10.96 (8.68, 13.04) vs. 12.45 (8.93, 16.30) at 72 hours after treatment, and 10.18 (8.68, 12.42) vs. 11.96 (8.81, 16.87) at 96 hours after treatment; APACHEⅡscore: 9.50 (5.75, 12.00) vs. 11.00 (6.25, 14.00) at 72 hours after treatment, and 10.00 (4.00, 12.00) vs. 12.00 (7.00, 14.75) at 96 hours after treatment; BISAP score: 2.35±1.03 vs. 2.76±1.10 at 72 hours after treatment, and 2.08±1.21 vs. 2.70±1.11 at 96 hours after treatment], the differences were statistically significant (all P < 0.05). In terms of complications, the incidence of pancreatic abscess in the late initiation group was significantly lower than that in the early initiation group [5.00% (2/40) vs. 20.00% (18/90)], but the incidence of abdominal compartment syndrome was significantly higher than that in the early initiation group [42.50% (17/40) vs. 13.33% (12/90)], the differences were statistically significant (all P < 0.05). In addition, the ICU treatment time in the early initiation group was significantly shorter than that in the late initiation group [days: 11.00 (6.00, 20.00) vs. 15.00 (9.75, 25.00), P < 0.05], and there were no statistically significant differences in hospitalization costs, length of stay and mortality between the two groups. Conclusions:CBP can effectively increase the level of blood calcium and decrease the level of lactic acid and inflammatory factors. Starting CBP within 24-48 hours after diagnosis of SAP can reduce WBC level and disease severity score faster, and reduce the occurrence of pancreatic abscess. Initiation of CBP within 24 hours after diagnosis of SAP can reduce the incidence of abdominal compartment syndrome and shorten the duration of ICU treatment.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Objective To investigate the effect of Angelica sinensis polysaccharide (ASP) on intestinal injury in septic rats by regulating the adenosine-monophosphate-activated protein kinase (AMPK)/Nod-like receptor protein 3 (NLRP3) pathway-mediated pyroptosis. Methods A rat model of sepsis was created using cecal ligation and perforation surgery. The successfully modeled rats were separated into a model group;low-,medium-,and high-ASP (ASP-L,ASP-M,ASP-H,respectively) groups;and an AMPK inhibitor group,with 12 rats in each group. Twelve rats in the same period were regarded as the sham group without cecal ligation. Hematoxylin and eosin staining was used to observe the pathological changes in the small intestine of the rats and pathological scoring was performed. TUNEL staining was used to detect intestinal cell pyroptosis;immunohistochemical staining was used to detect NLRP3 expression in small intestine tissue;Enzyme-linked immunosorbent asays were used to determine the serum levels of interleukin (IL)-18 and IL-1β and the activities of D-amino acid oxidase (DAO) and intestinal fatty acid binding protein (iFABP) in the small intestine;and Western blotting was used to determine the levels of gasdermin D (GSDMD),apoptosis-associated speck-like protein containing a CARD (ASC),cleaved caspase-1,and p-AMPK/AMPK proteins in small intestine tissue. Results Compared with the sham group,the model group showed increased small intestine tissue Chiu score;apoptosis rate;and NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1 and serum IL-18 and IL-1β levels and a decreased p-AMPK/AMPK ratio (P<0.05). Compared to the model group,the ASP-L,ASP-M,and ASP-H groups showed reduced small intestine tissue Chiu score;apoptosis rate;NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1,and serum IL-18 and IL-1β levels and an increased p-AMPK/AMPK ratio (P<0.05). AMPK inhibitors weakened the inhibitory effect of ASP on small intestine tissue cell apoptosis,and exacerbated intestinal injury (P<0.05). Conclusion ASP inhibited the activation of NLRP3 inflammasomes by activating AMPK expression,thereby inhibiting pyroptosis and alleviating intestinal injury in septic rats.

Objective To investigate the effect of Angelica sinensis polysaccharide (ASP) on intestinal injury in septic rats by regulating the adenosine-monophosphate-activated protein kinase (AMPK)/Nod-like receptor protein 3 (NLRP3) pathway-mediated pyroptosis. Methods A rat model of sepsis was created using cecal ligation and perforation surgery. The successfully modeled rats were separated into a model group;low-,medium-,and high-ASP (ASP-L,ASP-M,ASP-H,respectively) groups;and an AMPK inhibitor group,with 12 rats in each group. Twelve rats in the same period were regarded as the sham group without cecal ligation. Hematoxylin and eosin staining was used to observe the pathological changes in the small intestine of the rats and pathological scoring was performed. TUNEL staining was used to detect intestinal cell pyroptosis;immunohistochemical staining was used to detect NLRP3 expression in small intestine tissue;Enzyme-linked immunosorbent asays were used to determine the serum levels of interleukin (IL)-18 and IL-1β and the activities of D-amino acid oxidase (DAO) and intestinal fatty acid binding protein (iFABP) in the small intestine;and Western blotting was used to determine the levels of gasdermin D (GSDMD),apoptosis-associated speck-like protein containing a CARD (ASC),cleaved caspase-1,and p-AMPK/AMPK proteins in small intestine tissue. Results Compared with the sham group,the model group showed increased small intestine tissue Chiu score;apoptosis rate;and NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1 and serum IL-18 and IL-1β levels and a decreased p-AMPK/AMPK ratio (P<0.05). Compared to the model group,the ASP-L,ASP-M,and ASP-H groups showed reduced small intestine tissue Chiu score;apoptosis rate;NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1,and serum IL-18 and IL-1β levels and an increased p-AMPK/AMPK ratio (P<0.05). AMPK inhibitors weakened the inhibitory effect of ASP on small intestine tissue cell apoptosis,and exacerbated intestinal injury (P<0.05). Conclusion ASP inhibited the activation of NLRP3 inflammasomes by activating AMPK expression,thereby inhibiting pyroptosis and alleviating intestinal injury in septic rats.

Objective:To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma.Methods:Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 μm (small particle size) and 300~500 μm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results:The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P 1 month=0.012, P 3 month=0.009, P 6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant ( P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant ( P=0.182). Conclusions:In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.

Clinical data of 899 patients,who received colposcopic examination,were retrospectively analyzed.Both Reid's colposcopic index(RCI)score and biopsy were performed.The study showed that the value of RCI score was positively related to the severity of cervical lesions(F=2.043,P=0.03).The specificity of RCI for cervicitis,cervical intraepithelial neoplasia(CIN)Ⅰ were 98.8%,95.7% respectively;while sensitivity and negative predictive value for CIN Ⅱ,CIN Ⅲ were 77.7%,70.0%and 96.8%.97.4%,respectively.So RCI scoring can increase the diagnostic value of colposcope.

An effective method has been developed for laboratory scale production of IgG. Hybridomas were cultured in serum-free media with 2% IgG-free ascites. Cell density of up to 3.55 × 10 6cells/ml and antibody concentration of 135μ g/ml after purification were abtained, which is four time more than total production of that of IgG concentration in serum-free media. This in vitro method allows great improvement in antibodies production in batch tissue culture. The method reported here is easy to handle and is economical and universally adaptable.

Objective Evaluation of the benefit and safety of combined thrombolysis and precutaneous coronary intervention in acute myocardial infarction by retrospective analysis. Methods Precutaneous coronary intervention were performed in 45 patients with acute myocardial infarction immediately after thrombolysis. The clinical and angiographic data were compared with that of 31 patients with thrombolysis alone and 74 patients with primary precutaneous coronary intervention in the same period. Results Angiographic data showed that patients with PCI plus thrombolysis had more frequency of TIMI 3 flow than patients with thrombolysis alone (88.9% vs. 74.2%, P=0.087). Patients with PCI plus thrombolysis and with primary PCI had similar frequency of TIMI 3 flow (88.9% vs. 91.9% P=0.404). Clinical data showed that patients with PCI plus thrombolysis had less major adverse cardiovascular events in hospital than patients with thrombolysis alone (4.4% vs. 12.9%, P=0.181). Patients with PCI plus thrombolysis and with primary PCI had similar major adverse cardiovascular events (4.4% vs. 1.4%, P=0.319). Patients with three strategies of treatment had similar mortality (4.4% vs. 6.5% vs. 4.1%). Patients with three strategies of treatment had similar major bleeding events (4.4% vs. 3.2% vs. 1.4%) in hospital. Conclusion Combined thrombolysis and precutaneous coronary intervention maybe surpass thrombolysis alone, at least similar to primary PCI. This strategy of treatment is safe.