ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

BACKGROUND:With the increase of patients with cubital tunnel syndrome,ulnar groove plasty does not affect the normal anatomical structure and distribution of the ulnar nerve,which is one of the main surgical procedures for the treatment of cubital tunnel syndrome.3D printing combined with ulnar groove plasty can more accurately position the expansion depth and width of the ulnar groove to avoid some surgical complications. OBJECTIVE:To investigate the effect of 3D printing technology combined with ulnar groove plasty on nerve electrophysiology and prognosis in patients with cubital tunnel syndrome. METHODS:A total of 70 patients with moderate and severe cubital tunnel syndrome who were treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into two groups,with 35 cases in each group.The control group underwent traditional ulnar groove plasty.The observation group underwent 3D printing technology combined with ulnar groove plasty.The patients were followed up for 3 months.The clinical efficacy,latency,amplitude of compound muscle action potential of abductor pollicis brevis of the affected limb and ulnar nerve motor conduction velocity,grip strength on the affected side,pinch strength of the middle and thumb fingers,S-W monofilament of the little finger,two-point discrimination of the little finger,and Disabilities of the Arm,Shoulder and Hand Questionnaire score were compared between the two groups. RESULTS AND CONCLUSION:(1)Compared with the control group(74%),the excellent and good rate was significantly higher in the observation group(91%)(P<0.05).(2)Compared with pre-treatment,the latency of compound muscle action potential of abductor pollicis brevis of affected limb was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the two groups after treatment.The latency was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the observation group than those in the control group(P<0.05).(3)Compared with pre-treatment,the grip strength,middle finger and thumb pinch strength of the affected side,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly decreased in the two groups after treatment.The grip strength,middle finger and thumb pinch strength on the affected side were greater,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly smaller in the observation group than those in the control group(P<0.05).(4)Compared with pre-treatment,the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the two groups were significantly reduced after treatment,and the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the observation group were significantly lower than those of the control group(P<0.05).(5)It is concluded that 3D printing technology combined with ulnar groove plasty in the treatment of cubital tunnel syndrome can effectively improve its clinical efficacy,promote the neurophysiological recovery of patients,and enhance the function of fingers and upper limbs,which has high clinical application value.

Objective:To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats.Methods:UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results:Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion:Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective:To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness.Methods:A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model.Results:Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable.Conclusions:Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

Objective To explore the functional changes of the glial lymphatic system in patients with spontaneous intracerebral hemorrhage(sICH)by MR diffusion tensor imaging(DTI).Methods The clinical and imaging data of 32 sICH patients(sICH group)and 31 healthy volunteers(control group)were retrospectively collected,and the diffusivity values of DTI in different direc-tions were collected from all the subjects,the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index was calculated,the difference of DTI-ALPS index values between the sICH group and the control group was compared,the changes in the function of the glial lymphatic system in sICH patients were evaluated,and the correlation between DTI-ALPS index and clinical indi-cators in sICH patients was further analyzed.Results The DTI-ALPS index of cerebral hemispheres on the lesions side of sICH group was significantly lower than that on the unaffected side(P＜0.01,t=-5.03),and lower than that on the left side of control group(P＜0.01,t=-9.85)and the right side(P＜0.01,t=-8.80).In addition,vascular endothelial growth factor(VEGF)tes-ting was performed in 8 of the 32 patients,and the levels[(187.40±19.11)pg/mL]were significantly higher than the normal range(0-142.20 pg/mL).Conclusion Through the quantitative analysis of the DTI-ALPS index,the damage to the function of the glial lymphatic system of sICH can be reflected,and perhaps the mechanism of pathophysiological changes in the brain after sICH can be reflected from a new perspective by using MR DTI technology.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective To investigate the relationship between systemic immune-inflammation index(SII),red blood cell distribution width(RDW),albumin(ALB)ratio(RAR)and severity of disease and respiratory failure in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 110 patients with AECOPD were divided into the severe group(n=37)and the non-severe group(n=73).They were also divided into the respiratory failure group(n=26)and the non-respiratory failure group(n=84)according to whether they had respiratory failure.Platelet count(PLT),neutrophil count(NEU),lymphocyte count(LYM),RDW,ALB,SII and RAR were compared between different groups.Multiple Logistic regression method was used to analyze influencing factors of severe and concurrent respiratory failure.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of indicators for severe condition and respiratory failure.Results Compared with the non-severe group,there were increased NEU,SII,RDW and RAR,and decreased PLT and LYM in the severe group(P＜0.05).Compared with the non-respiratory failure group,there were increased NEU,SII,RDW and RAR,and decreased LYM and ALB in the respiratory failure group(P＜0.05).Multivariate Logistic regression analysis showed that increased SII and RAR were independent risk factors for severe condition or respiratory failure in patients with AECOPD.ROC curves indicated that the area under the curve(AUC)of SII combined with RAR for predicting severe condition and respiratory failure in patients with AECOPD were 0.882(0.806-0.935)and 0.908(0.837-0.954),both of which were higher than those of SII or RAR alone(P＜0.05).Conclusion Combination of SII and RAR can effectively help to evaluate the condition and the occurrence of respiratory failure in patients with AECOPD.

The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2％DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.