ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

Objective To investigate the impacts of midazolam(MDZ)on the proliferation,migration,and invasion of esophageal cancer(EC)cells by regulating the monocyte chemotactic protein-1(CCL2)-C-C chemokine receptor 2(CCR2)signaling pathway.Methods QRT-PCR method was applied to determine the expression of CCL2 and CCR2 mRNA in EC tissue,adjacent cancer tissue,human normal esophageal epithelial cell HEEC,and EC cell Eca-109.MTT assay and colony formation were applied to measure cell proliferation.Scratch test,Transwell test,and TUNEL method were applied to determine cell migration,invasion,and apoptosis,respectively.The expression of CCL2-CCR2 signaling pathway proteins was determined using Western blot method.Results Compared with adjacent cancer tissues and normal human esophageal epithelial cells(HEEC),the mRNA and protein expression levels of CCL2 and CCR2 in cancer tissues and Eca-109 cells were increased(P＜0.05).Compared with the control group,the OD450 value,colony formation number,scratch healing rate,and invasive cell count of Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased,while the proportion of TUNEL positive cells increased(P＜0.05).Compared with the MDZ-H group,the OD450 value,colony formation number,scratch healing rate,and number of invasive cells in the MDZ-H+GW0742 group all increased,while the proportion of TUNEL positive cells decreased(P＜0.05).Compared with the control group,protein and mRNA expressions of CCL2 and CCR2 proteins in Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased(P＜0.05).Compared with the MDZ-H group,the MDZ-H+GW0742 group showed an increase in the expression of CCL2 and CCR2 proteins in Eca-109 cells(P＜0.05).Conclusion MDZ can inhibit the proliferation,migration,and invasion of EC cells by inhibiting the activation of the CCL2-CCR2 signaling pathway.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

Objective To investigate the impacts of midazolam(MDZ)on the proliferation,migration,and invasion of esophageal cancer(EC)cells by regulating the monocyte chemotactic protein-1(CCL2)-C-C chemokine receptor 2(CCR2)signaling pathway.Methods QRT-PCR method was applied to determine the expression of CCL2 and CCR2 mRNA in EC tissue,adjacent cancer tissue,human normal esophageal epithelial cell HEEC,and EC cell Eca-109.MTT assay and colony formation were applied to measure cell proliferation.Scratch test,Transwell test,and TUNEL method were applied to determine cell migration,invasion,and apoptosis,respectively.The expression of CCL2-CCR2 signaling pathway proteins was determined using Western blot method.Results Compared with adjacent cancer tissues and normal human esophageal epithelial cells(HEEC),the mRNA and protein expression levels of CCL2 and CCR2 in cancer tissues and Eca-109 cells were increased(P＜0.05).Compared with the control group,the OD450 value,colony formation number,scratch healing rate,and invasive cell count of Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased,while the proportion of TUNEL positive cells increased(P＜0.05).Compared with the MDZ-H group,the OD450 value,colony formation number,scratch healing rate,and number of invasive cells in the MDZ-H+GW0742 group all increased,while the proportion of TUNEL positive cells decreased(P＜0.05).Compared with the control group,protein and mRNA expressions of CCL2 and CCR2 proteins in Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased(P＜0.05).Compared with the MDZ-H group,the MDZ-H+GW0742 group showed an increase in the expression of CCL2 and CCR2 proteins in Eca-109 cells(P＜0.05).Conclusion MDZ can inhibit the proliferation,migration,and invasion of EC cells by inhibiting the activation of the CCL2-CCR2 signaling pathway.

This study aims to assess the efficacy and safety of Hulisan Capsules in the treatment of knee osteoarthritis, which is expected to serve as a reference for clinical practice. To be specific, randomized controlled trial(RCT) on the treatment of knee osteoarthritis with Hulisan Capsules was retrieved from EMbase, PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, SinoMed, and VIP(from inception to November 15, 2021). Two researchers independently screened the articles, extracted the data, and evaluated the risk of bias with ROB. RevMan 5.4 was used for Meta-analysis. Finally, 12 RCTs were screened out, involving 1 703 cases(1 075 in the experimental group and 628 in the control group). Meta-analysis showed that conventional treatment + Hulisan Capsules was superior to conventional treatment alone in terms of symptom relief rate(RR=1.19, 95%CI[1.09, 1.30], P<0.000 1), Lysholm score(MD=11.17, 95%CI[7.35, 15.00], P<0.000 01), visual analogue scale(VAS) score(MD=-0.99, 95%CI[-1.30,-0.68], P<0.000 01), and knee function score(RR=8.94, 95%CI[6.51, 11.37], P<0.000 01). Hulisan Capsules alone was superior to the conventional treatment alone in terms of the symptom relief rate(RR=1.38, 95%CI[1.13, 1.69], P=0.002) and knee function score(MD=2.88, 95%CI[0.81, 4.94], P=0.006), but VAS score was insignificantly different between the patients treated with Hulisan Capsules alone and those with conventional treatment alone(MD=-0.57, 95%CI[-1.42, 0.29], P=0.19). Hulisan Capsules + conventional treatment showed insignificant difference in symptom relief rate from the Zhuifeng Tougu Capsules + conventional treatment(RR=1.07, 95%CI[0.91, 1.25], P=0.44). The Lequesne score was insignificantly different between Hulisan Capsules + conventional treatment and conventional treatment/Zhuifeng Tougu Capsules + conventional treatment(MD=-2.17, 95%CI[-6.29, 1.96], P=0.30). The incidence of adverse reactions in the experimental group was significantly lower than control group(RR=0.57, 95%CI[0.34, 0.96], P=0.03). According to the available data and methods, Hulisan Capsules/Hulisan Capsules + conventional treatment could improve the symptom relief rate, Lysholm score, knee function score, and VAS score of patients with knee osteoarthritis, and alleviate the symptoms of pain, stiffness, and swelling of them. No serious adverse reactions were found yet. In the future, more large-sample and standard clinical trials are needed to verify the effect and safety of Hulisan Capsules in the treatment of knee osteoarthritis.
Humans ; Osteoarthritis, Knee/drug therapy* ; Capsules ; Pain

Objective:To observe and compare the clinical effect of single-incision and two-incision posterior chamber phakic intraocularlens implantation in the correction of extreme myopia.Methods:40 cases(80 eyes) of patients with extreme myopia underwent conventional two-incision posterior chamber phakic intraocularlens implantation in our hospital from January 2011 to June 2013 were selected as the control group and 40 cases(80 eyes) underwent single-incision posterior chamber phakic intraocularlens implantation from July 2013 to January 2016 were selected as observation group.The open hole before and after operation,best corrected visual acuity of vision,operation safety,effectiveness index,diopter (column mirror,equivalent ball for eyeglasses),intraocular pressure,ECD,anterior chamber depth and occurrence of complications were compared between two groups.Results:The uncorrected visual acuity (UCVA) of both groups at 6 months after operation were significantly higher than those before operation (P＜0.05),which was significantly higher in the observation group than that of the control group (P＜0.05);The operation safety and effectiveness index of observation group were significantly higher than those of the control group (P＜0.05);The cylinder and spherical equivalent degree of both groups at 6 months after operation were significantly better than those before operation(P＜0.05),which was significantly better in the observation group than that of the control group(P＜0.05).The corneal endothelial cell counts(ECL) of control group after operation was significantly lower than that before operation (P＜0.05),and no significant difference was found in the ECL of observation group before and after operation (P＞0.05).The ECL of observation group after operation was significantly higher than that of the control group (P＜0.05);The incidence rate of complication in observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Compared with two-incision operation,the single-incision posterior chamber phakic intraocularlens implantation had remarkable clinical effect in the correction of extreme myopia with higher security.

Objective To investigate the efficacy and strategy of percutaneous laser disc decompression (PLDD) for patients with multisegmental lumbar disc herniation. Methods Between December 2005 and December 2008,a total of 56 patients with multisegmental lumbar disc herniation underwent PLDD. Under local anesthesia, the operation was performed using Nd:YAG laser. A digital subtraction angiography (DSA) system was employed to guide the surgery,insert burning, each 1 s, pulse intermission gasification 1 s, single segment laser total 400-800 J. In preoperative and postoperative 3 months visual analogue scale(VAS) and Oswestry disability index (ODI) scores of times during followed up,Macnab standard to assess the clinical curative effect. Results The patients were followed up for 6 - 36 months (mean 18 months). The ODI improved from (31.10 ±2.92) scores to (11.80 ±2.62) scores (t=3.067,P ＜0.01 ). The VAS also showed postoperative improvement of pain compared with preoperative findings (7.00 ± 1.41 ) scores vs (3.00 ± 0.81 ) scores (t= 2.802,P ＜0.01 ). According to the Macnab standard, 36 patients achieved excellent outcomes, 10 were good, 8 were fair, and 2 were poor. The rate of excellent and good outoomes was 82. 1% (46/56). No patient had postoperative complications. Conclusions PLDD is effective and safe for patients with multisegmental lumbar disc berniation. The cases recover quickly after the operation, because the procedure is minimally invasive.