ObjectiveTo evaluate the effectiveness and safety of Sufei Pingchuan Formula （肃肺平喘方） in the treatment of bronchiectasis with airflow limitation， phlegm-heat obstructing the lung， and lung-spleen qi deficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 72 patients with stable bronchiectasis with airflow limitation of phlegm-heat obstructing the lung and lung-spleen qi deficiency syndrome were randomly divided into treatment group and control group， with 36 cases in each group. On the basis of regular inhalation of tiotropium bromide inhalation spray， the treatment group was given Sufei Pingchuan Formula granules， and the control group was given Sufei Pingchuan Formula granule simulant. The course of treatment in both groups was 12 weeks. The pulmonary function of both groups before and after treatment was observed， specifically focusing on forced expiratory volume in one second （FEV1）； the modified British Medical Research Council （mMRC） dyspnea scale， 24-hour sputum volume， COPD assessment test （CAT）， and traditional Chinese medicine （TCM） syndrome scores were assessed before treatment and after 4， 8， and 12 weeks of treatment； acute exacerbations were recorded at weeks 4， 8， and 12； additionally， changes in routine blood tests， urinalysis， liver and kidney function， and adverse events were monitored before and after treatment. ResultsAfter treatment， 4 patients in the treatment group and 6 in the control group dropped out. After 12 weeks of treatment， FEV1 increased in both groups compared to pre-treatment levels （P＜0.05）， but the difference between groups was not statistically significant （P＞0.05）. Compared to before treatment， the treatment group showed a reduction in mMRC scores after 12 weeks （P＜0.05） and a decrease in 24-hour sputum volume， CAT scores， and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）. In the control group， 24-hour sputum volume decreased after 12 weeks （P＜0.05）， and TCM syndrome scores decreased at weeks 8 and 12 （P＜0.05）. Compared to the control group， the treatment group showed a greater reduction in mMRC scores at week 12 （P＜0.05）， a decrease in 24-hour sputum volume and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）， and lower CAT scores at weeks 8 and 12 （P＜0.05）. The frequency and number of acute exacerbations in the treatment group were significantly lower than those in the control group at week 12 （P＜0.05）. No severe adverse events occurred in either group. ConclusionSufei Pingchuan Formula can improve the pulmonary function FEV1， the severity of dyspnea， reduce 24-hour sputum volume and frequent acute exacerbations， and improve the quality of life in patients with bronchiectasis and airflow limitation， with good safety.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Objective To analyze the factors influencing the occupational health literacy (OHL) level among workers in key industries from the perspectives of both individual workers and enterprises. Methods A total of 32 336 front-line workers from 12 key industries in the secondary industry in Guangdong Province were selected as the research subjects by a stratified cluster random sampling method. Their OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations, and the influencing factors were analyzed. Results The OHL level of the research subjects was 48.5%. The OHL level of the research subjects in four dimensions from high to low was basic knowledge of occupational health protection, occupational health practice and behavior, legal knowledge of occupational health, and basic skills of occupational health protection (80.7%, 61.2%, 48.3% and 29.5%, respectively). The multivariable logistic regression analysis showed that the OHL level of female workers was lower than that of males (P<0.05). Lower OHL was also associated with older age, lower education level, lower personal monthly income of workers (all P<0.01). The workers with length of service < 3 years and ≥ 20 years had lower OHL level than those with length of service 3-<10 years and 10-<20 years, respectively (all P<0.05). Workers in larger enterprises had higher OHL levels (all P<0.01). The OHL level of workers in the sixth category of industries with occupational injuries had higher occupational injury risks than those in the third and fourth categories (all P<0.05). The OHL levels of workers in state-owned enterprises, private enterprises, foreign-funded enterprises, and other enterprises were higher than that of workers in public institutions (all P<0.05). Conclusion The influencing factors of workers′ OHL in key industries of the secondary industry include individual factors (gender, age, education level, personal monthly income, length of service) and enterprise factors (enterprise size, enterprise nature and industry injury risk category). Female, older workers, those with lower education or income, and those with short length of service represent priority groups for OHL interventions, while small and micro enterprises are priority units for future workplace health promotion intervention.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.

Aim To establish a reliable in vitro evaluation sys-tem to assess human liver UGTs activities and the inhibitory effect of drugs on human liver UGTs and validate its accuracy and stability.Methods Six probe substrate of the six major subtypes of human liver microsomal UGT enzymes were select-ed.The activity of human liver microsomal UGT enzymes was determined under optimized incubation conditions using a metab-olite generation method.The concentrations of metabolites were determined using a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Known inhibitors were used to verify the established incubation system.Results The estab-lished LC-MS/MS analysis method complied with the require-ments of bioanalysis.In the incubation system of this experi-ment,known UGT inhibitors exhibited significant inhibitory effects.Conclusions This study successfully establishes an ac-curate and reliable in vitro evaluation system,which can be used to assess the in vitro inhibition of drugs on UGT enzymes,provi-ding important guidance for drug development and rational clini-cal medication.

Objective To explore clinical effect of allogeneic peroneal bone marrow support combined with plate internal fixation in treating Neer type Ⅳ proximal humeral fractures.Methods From December 2017 to December 2020,12 patients with Neer type Ⅳ proximal humeral fractures were treated with allogeneic peroneal bone marrow support combined with plate internal fixation,including 7 males and 5 females,aged from 56 to 78 years old;the time from injury to operation ranged from 1 to7 days.Operative time,fracture healing time and complications during follow-up were observed,and clinical efficacy was e-valuated by Constant-Murley score at the latest follow-up.Results All patients were obtained follow up for 20 to 29 months.All patients got bone healing and incisicons were healed at stage Ⅰ,operative time ranged from 95 to 138 min,blood loss ranged from 210 to 275 ml,fracture healing time ranged from 14 to 18 weeks.Two patients occurred postoperative shoulder stiffness and recovered after 2 weeks of passive exercise.There were no complications such as infection,poor wound healing,and fail-ure(fracture and loosening)of internal fixators occurred.Constant-Murley shoulder function score ranged from 69 to 89 at the latest follow up,2 patients got excellent results,9 good and 1 fair.Conclusion The application of allogeneic fibular bone mar-row placement could provide effective support for medial humerus,which is conducive to assisting reduction of fracture end,re-ducing occurrence of internal fixation failure caused by collapse of humerus head and screw perforation,and significantly im-proving function of shoulder joint.

Objective:To investigate the impact of syringin on lung tissue injury in acute respiratory distress syndrome(ARDS)rats by regulating miR-124-3p/mitogen-activated protein kinase 14(MAPK14)axis.Methods:ARDS rat model was established by intratracheal instillation of LPS(1 mg/kg,500 μl),and the successfully modeled rats were divided into ARDS group,syringin-L group(syringin 17.5 mg/kg),syringin-M group(syringin 35 mg/kg),syringin-H group(syringin 70 mg/kg),miR NC group(syringin 70 mg/kg+miR NC)and miR-124-3p inhibitor group(syringin 70 mg/kg+miR-124-3p inhibitor),with 12 rats in each group.Another 12 rats were instilled with 500 μl of normal saline in the trachea as a control group.Each administration group was injected with corre-sponding dose of syringin by intraperitoneal injection,miR NC group and miR-124-3p inhibitor group were administered with miR NC and miR-124-3p inhibitor by tail vein injection respectively,and control group and ARDS group were injected with corresponding dose of normal saline,for 3 consecutive days.RT-qPCR was applied to detect expressions of miR-124-3p and MAPK14 mRNA in lung tissue;HE staining was applied to observe lung histopathology;a blood gas analyzer was used to detect PaO2 and FiO2 in rat arterial blood,and to calculate PaO2/FiO2;ELISA was applied to detect levels of IL-1β,IL-18 and TNF-α in rat bronchoalveolar lavage fluid;Western blot was applied to detect expressions of MAPK14 and high mobility group box protein(HMGB1);dual-luciferase reporter gene assay was applied to analyze the relationship between miR-124-3p and MAPK14.Results:Compared with control group,expression of miR-124-3p in ARDS group was decreased(P<0.05),and the lung tissue structure was unclear,pulmonary interstitial congestive edema,inflammatory cell infiltration,and obvious lung tissue damage were observed,arterial blood PaO2,PaO2/FiO2 were decreased(P<0.05),the lung injury score and expression of MAPK14 mRNA in lung tissue,W/D value,levels of IL-1β,IL-18 and TNF-α in bron-choalveolar lavage fluid,and protein expressions of MAPK14 and HMGB1 were greatly increased(P<0.05);compared with ARDS group,expression of miR-124-3p in syringin-L group,syringin-M group and syringin-H group were greatly increased,the lung tissue damage was alleviated,arterial blood PaO2,PaO2/FiO2 were increased,the lung injury score and expression of MAPK14 mRNA in lung tissue,W/D value,levels of IL-1β,IL-18 and TNF-α in bronchoalveolar lavage fluid,and protein expressions of MAPK14 and HMGB1 were greatly decreased(P<0.05);down-regulation of miR-124-3p could increase MAPK14 expression,and attenuate the inflammatory inhibitory and lung-protective effects of syringin on ARDS rats.Conclusion:Syringin can alleviate lung injury in ARDS rats by regulating the miR-124-3p/MAPK14 axis.

Objective:To investigate the clinical features,gene mutation profile,efficacy and prognostic factors of primary extranodal diffuse large B-cell lymphoma(EN-DLBCL).Methods:A retrospective analysis was performed for 382 patients with primary EN-DLBCL with complete clinical data who were treated in West China Hospital from January 2013 to January 2023,and their clinical characteristics,gene mutation profile,efficacy and prognostic factors were analyzed.Results:The median age of the 382 patients with EN-DLBCL was 56 (18-89 )years old.The male-to-female ratio was 1.12∶1,and the most common primary sites were gastrointestinal tract (31.7％),Wechsler ring (19. 1％)and breast gland (7.1％).A total of 51 gene mutations were fund,and the most common frequencies of gene mutations were TP53 (32.5％),MYD88 (32.5％),and CD79B (30.0％).The median follow-up was 63 months,and the 5-year progression-free survival (PFS)rate was 74.5％ and the 5-year overall survival (OS)rate was 89.6％. The adverse factors on PFS were as follows:>1 extranodal sites involvement (P<0.001),P53≥50％(P<0.001),hyper double expression(hDEL)of C-myc>50％/Bcl-2>70％(P<0.001).The adverse factors affecting the OS of patients were as follows:>1 extranodal sites involvement (P<0.001),P53≥50％(P<0.001),hDEL(P<0.001). Chemotherapy combined with local radiotherapy could improve PFS (P=0.041)and OS (P=0.003),while R-CHOP+X (molecule agents as BTKi、HDACi、Lenalidomide)failed to show a significant difference in PFS (P=0.075)and OS (P=0.767 ).Among the 40 patients who underwent next-generation sequencing at high risk,there was no significant in PFS (P=0.849)and OS (P=0.500)of patients with positive MYD88 and/or CD79B mutations (MCD subtype)treated with BTKi and patients with negative MYD88 and CD79B mutations.Conclusion:Primary EN-DLBCL can involve multiple organs or tissue sites.TP53,MYD88,and CD79B are the most common gene mutations.The efficacy of BTKi in patients with positive MCD subtypes at intermediate and high risk is not inferior to that in MCD-negative control patients.

Objective:To investigate the predictive value of MRI balanced steady-state free precession(b SSFP)synergistic voxel incoherent motion diffusion weighted imaging(IVIM-DWI)and Gd-DTPA enhanced scanning for the status of extramural vascular invasion(EMVI)in rectal cancer before surgery.Methods:A total of 105 rectal cancer patients from the People's Hospital of Lujiang County,Anhui Province,were retrospectively selected and included.All patients were confirmed by postoperative pathology and underwent preoperative b SSFP sequences,IVIM-DWI functional imaging,and Gd-DTPA-enhanced multiparameter MRI scans.Three seven-point schemes based on individual b SSFP sequences,IVIM-DWI functional imaging,and Gd-DTPA en-hancement,two-by-two synergy,and multi-sequence combined diagnosis were utilized in con-junction with conventional MRI sequences for preoperative prediction of EMVI status.The diag-nostic efficacy of T2WI and b SSFP sequences was compared with that of postoperative patho-logic results.ROC curves were plotted to obtain the corresponding area under the ROC curve(AUC),specificity,and sensitivity.Results:The AUC for predicting the preoperative vascular status outside the rectal wall was 0.572(95％CI:0.408～0.737)for the conventional T2 lipid sup-pression sequence,with a specificity of 0.811 and a sensitivity of 0.667.The AUC for the b SSPF sequence was 0.817(95％CI:0.680～0.954),with a specificity of 0.900 and a sensitivity of 0.733.All of the statistical parameters were higher than the diagnostic efficacy of conventional T2 lipid suppression sequences.The multi-sequence MRI co-diagnosis had an AUC of 0.961(95％CI:0.886～1.000),with a specificity of 0.988 and a sensitivity of 0.875(P＜0.05).Conclusion:Mag-netic resonance b SSFP sequence synergized with IVIM-DWI and Gd-DTPA-enhanced multipa-rameter scanning has high clinical application value for the preoperative prediction of EMVI inva-sion in rectal cancer.