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 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.

Background Subways are typical congregate settings and may facilitate aerosol transmission of viruses. However, quantified transmission probability estimates are lacking. Purpose To model spread and diffusion of respiratory aerosols in subways by simulation and calculation of infection probabilities. Methods The internal environment of carriages of Shanghai Metro Line 10 was used to establish a study scene. The movement of tiny particles was simulated using the turbulent model. Trend analysis of infection probabilities and viral quantum doses was conducted in a closed subway carriage scene by a quantum emission-infection probability model. Results Under a typical twelve-vent air conditioning configuration, respiratory droplet aerosols within a subway carriage dispersed rapidly throughout various regions due to airflow, with limited short-term diffusion to other carriages. Concurrently, owing to the uncertainty of airflow patterns, the airflow might circulate and converge within carriages, causing delayed outward dispersion or hindered dispersion of droplet aerosols upon entry into these zones. Passengers boarding the carriage could exacerbate the formation of these zones. When the air conditioning system functioned adequately (air exchange rate=23.21 h⁻¹), the probability of a virus carrier transmitting the virus to other passengers within the same carriage via aerosol transmission was approximately 3.8%. However, in the event of air conditioning system failure (air exchange rate=0.5 h⁻¹), this probability escalated dramatically to 30%. Furthermore, a super-spreader (with virus spreading exceeding 90% of the average) elevated the infection probability to 14.9%. Additionally, due to the complexity of turbulence within the carriage, if local diffusion occurred in 1/2 zones of a carriage, the anticipated infection probability would increase to 8.9%, or during the morning or evening rush hours leading to elevated aerosol concentrations, the infection probability would rise to 4.7%. The subway transmission probability for common coronaviruses diminished to as low as 0.9%. Conclusion Combined computational fluid dynamics and infection probability analysis reveals that in the prevalent twelve-vent air conditioning configurations, despite being a major transportation hub with substantial spatial-temporal overlap, the internal space of subway carriages exhibits a certain level of resistance to virus aerosol transmission owing to built-in ventilation capabilities. However, turbulence and passenger positioning may lead to localized hovering of droplet aerosols, thereby increase the risk of virus transmission. Furthermore, super-spreaders, poor operational status of built-in air conditioning system, and high passenger volume at morning or evening peak hours exert profound effects on virus transmission and infection probability.

Gastrointestinal stromal tumour (GIST) is a common mesenchymal tumour arising in the gastrointestinaltract, but not frequently encountered in the rectum. Herein, we describe a case of a rectal GISTwhich mimicked histomorphological features of a schwannoma; thus, making intraoperative frozensection evaluation challenging. Although subsequent immunohistochemistry and molecular findingsreadily confirmed the diagnosis of a GIST, we wish to draw attention to three clues that will help thepathologist steer clear of this potential diagnostic pitfall. One, GISTs are relatively more commonthan schwannomas in the rectum. Two, schwannomas usually have very little mitoses. Three,rectal GISTs commonly exhibit nuclear palisades. We also discuss the diagnostic, prognostic andtherapeutic functions of immunohistochemical and molecular investigations. As the surgical intentfor rectal GISTs is for en-bloc excision with wide margins, we surmise that the intraoperative consultshould include GIST as a possible differential diagnosis for rectal mesenchymal tumours. In view ofthe potential for neoadjuvant treatment with imatinib before surgical excision to preserve sphincterfunction, a multidisciplinary approach is recommended for establishing most effective treatmentstrategy in these rare complex cases.

Objective To discuss the efficiency and safety of thalidomide combined with mFOLFOX in trea-ting advanced colon cancer.In addition,to observe the influence of mFOLFOX combined with thalidomide on serum vascular endothelial growth factor(VEGF)leveles.Methods One hundred patients with advanced colon cancer were divided randomly into two groups by digital table method.In the combined group,fifty patients were treated by mFOL-FOX combined with thalidomide.In the control group,fifty patients were treated by mFOLFOX alone.All the patients were tested serum VEGF before and after four cycle of chemotherapy.Results The response rate was 42% in the combined group vs.38% in the control group.Higher clinical benefit rate was found in the combined group (78% vs. 68%).The median time to progression(TTP)was 110 days vs.107 days.The differents between the two groups were not statistically significant(all P >0.05).After treatment of 4 cycles,the serum VEGF concentration of combined group and control group were respectively(317.40 ±55.54)ng/L and (330.84 ±64.48)ng/L,which were signifi-cantly decreased compared with pretreafment.The combination group decreased more obviously,the difference between the two groups were statistical significance(t =11.634,P =0.000).Conclusion Combined thalidomide with mFOL-FOX can′t improved clinical curative effect on the advanced colon cancer significantly.However,thalidomide can re-duce the levels of serum VEGF,and improve the quality of life.