ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Polymyxins are the first-line drugs used in multidrug resistance(MDR)Gram-negative infections.Polymyxin-induced nephrotoxicity is the major dose-limiting factor hindering its clinical use.It has been suggested that the mechanism of polymyxin-associated nephrotoxicity is related to its accumulation in the kidney upon extensive reabsorption from renal proximal tubular cells,and one or more renal transporters may mediate the process that polymyxins enter the renal tubular cells across cytomembrane.This review aimed to describe the roles of renal transporters in polymyxins reabsorption into the renal tubular cells and provide reference for reducing the nephrotoxicity of polymyxin.

Fermentum Rubrum（FR） is a kind of traditional Chinese medicine with dual-use functions of medicine and food， which has been used for more than 1 000 years. By referring to the ancient herbal classics and modern laws and regulations， the author sorted out the origin of FR， sorted out the development of processing， and analyzed the problems existing in the quality standard， aiming to provide a basis for further research and development of FR. There are many theories about the origin of FR. After summarizing and sorting out the relevant literature， three viewpoints are mainly drawn， including Han dynasty origin theory， Wei and Jin origin theory and Tang dynasty origin theory. After synthesizing the views of various schools， it is believed that the origin of FR should be no later than the Eastern Han dynasty. FR is made from rice by fermentation， which has the effect of strengthening the spleen， eliminating food， promoting blood circulation and removing stasis after fermentation. Although the natural fermentation in ancient times has been able to pay attention to the influence of temperature， humidity and strain on the quality of FR， due to the low level of science and technology， there are still problems such as complicated and cumbersome process， large workload and high labor cost. To the pure fermentation in modern times， the fermentation processing method of FR has been evolved， gradually improved and perfected. However， due to the lack of standardized research， there is no unified standard for the fermentation process of FR in various regions， and the quality standard lags behind seriously， which leads to the unstable product quality on the market. Among the 15 specifications for the preparation of FR， only 6 have been published in the past 5 years， and most of them have not been revised in a timely manner， and some of them have not been included in the updated version. Based on this， it is recommended to carry out a systematic study on processing technology of FR， and the best process is selected to accelerate the revision and improvement of its standardization， so as to improve the quality of FR sold in the market and promote its stable and sustainable development.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

Tumor-associated tertiary lymphoid structures(TLSs)are ectopic lymphoid formations within tumor tissue,with mainly B and T cell populations forming the organic aggregates.The presence of TLSs in tumors has been strongly associated with patient responsiveness to immunotherapy regimens and improving tumor prognosis.Researchers have been motivated to actively explore TLSs due to their bright clinical application prospects.Various studies have attempted to decipher TLSs regarding their formation mechanism,structural composition,induction generation,predictive markers,and clinical utilization.Meanwhile,the scientific approaches to qualitative and quantitative descriptions are crucial for TLS studies.In terms of detection,hematoxylin and eosin(H&E),multiplex immunohistochemistry(mIHC),multiplex immunofluorescence(mIF),and 12-chemokine gene signature have been the top approved methods.However,no standard methods exist for the quantitative analysis of TLSs,such as absolute TLS count,analysis of TLS constituent cells,structural features,TLS spatial location,density,and maturity.This study reviews the latest research progress on TLS detection and quantification,proposes new directions for TLS assessment,and addresses issues for the quantitative application of TLSs in the clinic.

Leptin, a peptide hormone discovered in the 1990s, arouses interest as it can regulate the body′s metabolism. In recent years, many studies have shown that leptin can promote the proliferation, activation and cytokine synthesis of various immune cells, and participate in innate and adaptive immune responses. This article reviewed the role of leptin and involved signaling pathways in immune response and the potential of leptin as a vaccine adjuvant.

Objective To investigate the inhibition effect of liraglutide (lira) on high glucose-induced adhesion of endothelial cells to monocyte.Methods Human umbilical vascular endothelial cells (HUVECs) induced by high glucose (20 mmol/L) were incubated with different concentrations of liraglutide (0,0.3,3,30 nmol/L) for different time.THP-1 cells were pre-labeled with Calcein-AM and then incubated with HUVECs for 1 h,M199 medium were used for washing the nonadherent cells for 3 times,and the adhesion of HUVECs to THP-1 cells were measured by Fluorence microplate reader;real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were employed to detect the mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1),respectively.Western blot was used to measure the content of IκBα,p-IκBα and the distribution of p65 in plasma and nuclear.GST-IκBα was introduced as substrate to test the activity of IκB-kinase (IKK).Results The adhesion of HUVECs to THP-1 (P ＜ 0.01),the mRNA and protein expression of VCAM-1 and ICAM-1 (P ＜ 0.05,P ＜ 0.01),the phosphorylation of κBα (P ＜ 0.05,P ＜ 0.01),the translocation of p65 subunit from plasma to nuclear and the activity of IKK (P ＜ 0.01) in HUVECs were all elevated by stimulation with 20 mmol/L glucose,and the content of IκBα was decreased accordingly (P ＜0.01).Pre-incubation with lira could reverse the above effect of high concentration of glucose.Conclusions Lira could reduce VCAM-1 and ICAM-1 expression through IKK/NF-κB pathways in 20 mmol/L glucose-induced HUVECs,which finally suppress THP-1-HUVECs adhesion.

[Objective]To investigate the efficacy of total hip arthroplasty(THA)on the treatment of traumatic arthritis that caused by internal fixation failures of intertrochanteric fractures.[Methods]During January 2009 and March 2016,35 cases of trau?matic arthritis(male:18 cases;female17 cases;49 ~ 86 years old,with an average age of 68.5 years)caused by internal fixation failures or malunion of intertrochanteric fractures,were undergo THA. Among 35 cases,13 cases were performed with the proximal femoral fixation stems,10 cases were with distal fixation stems,and 12 cases were with extended stems.[Results]With 3~65 months follow-up,the hip joint HSS score was elevated from 44.1(31 ~ 65)preoperative to 82.5(58 ~ 94)postoperative without obvious loosening. No postoperative deep infectionwas found. The femoral stems in 2 cases were found to sink 5 mm and 10 mm,respectively. No obvious prosthesis loosening was found. Taken together ,the satisfaction rate of THA on the joint function of traumatic arthritis was 91.4%.[Conclusion]Total hip arthroplasty is recommended as an effective approach for treating traumatic arthritis caused by internal fixation failures of intertrochanteric fractures. Distal fixed prosthesis was recommended due to bone sclerosis or defects of proximal femur. Coupled with emphasis on reconstruction of the greater trochanter ,good therapeutic effects could be achieved.

Objective To reconstruct the perfusion parameters of murine hindlimbs peripheral tissue by using fluorescence reflectance imaging technique. Methods BALB/c mice were injected with intravenous bolus injection of indocyanine green (ICG) (10μg) into the tail vein. Time-series fluorescence intensity images were obtained for 200 s immediately after the injection. After the serial imaging, silhouette images of the mice were taken under white light to obtain the region of interest (ROI) of the murine hindlimbs. Bi-exponential model was applied to analyze the dynamic fluorescence parameters and the peripheral tissue perfusion parameter images were reconstructed. Results The fitted perfusion curves obtained from bi-exponential model were in good agreement with the measured ones. The parametric images which reflected the vascular sufficiency of murine hindlimbs were reconstructed. Conclusions A novel method for parametric images of murine hindlimbs peripheral tissue blood perfusion is proposed in this paper, which is noninvasive with higher resolution and little damage to biological tissues.