Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg^-1 bleomycin. The successfully modeled rats were randomly divided into a blank group， a model group， a prednisone （3.15 mg·kg^-1） group， and low-dose， medium-dose， and high-dose groups of Wuwei Shenqintang （4.586， 9.172， 18.344 g·kg^-1）. The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin （HE） staining was used to measure the pathological changes in lung and colon tissue， and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， IL-6， IL-8， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （SIgA） in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of type Ⅰ collagen （Col-Ⅰ）， fibronectin （FN）， and alpha smooth muscle actin （α-SMA） in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang， screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang， and perform pathway enrichment analysis. ResultsCompared with the blank group， the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue， colonic mucosal damage， and connective tissue hyperplasia. The expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased （P<0.01）. The expression of Col-Ⅰ， FN， and α-SMA proteins and mRNAs in lung tissue was significantly upregulated （P<0.01）. Compared with the model group， the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue， alleviated colonic damage， decreased expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus （P<0.01）， and reduced average absorbance values and mRNA expression of Col-Ⅰ， FN， and α-SMA in lung tissue （P<0.05， P<0.01）， with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group， the model group had 19 significantly different compounds （P<0.05， P<0.01）. Wuwei Shenqintang could normalize 17 of these compounds compared with the model group （P<0.05， P<0.01）. Fecal metabolomics results showed that compared with those in the blank group， there were 42 compounds with significant differences in the model group （P<0.05， P<0.01）. Compared with the model control group， Wuwei Shenqintang could normalize 41 of these compounds （P<0.05， P<0.01）. The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine， tyrosine， and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis， which may be related to the regulation of the "lung-intestine axis".

ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg^-1 bleomycin. The successfully modeled rats were randomly divided into a blank group， a model group， a prednisone （3.15 mg·kg^-1） group， and low-dose， medium-dose， and high-dose groups of Wuwei Shenqintang （4.586， 9.172， 18.344 g·kg^-1）. The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin （HE） staining was used to measure the pathological changes in lung and colon tissue， and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， IL-6， IL-8， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （SIgA） in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of type Ⅰ collagen （Col-Ⅰ）， fibronectin （FN）， and alpha smooth muscle actin （α-SMA） in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang， screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang， and perform pathway enrichment analysis. ResultsCompared with the blank group， the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue， colonic mucosal damage， and connective tissue hyperplasia. The expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased （P<0.01）. The expression of Col-Ⅰ， FN， and α-SMA proteins and mRNAs in lung tissue was significantly upregulated （P<0.01）. Compared with the model group， the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue， alleviated colonic damage， decreased expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus （P<0.01）， and reduced average absorbance values and mRNA expression of Col-Ⅰ， FN， and α-SMA in lung tissue （P<0.05， P<0.01）， with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group， the model group had 19 significantly different compounds （P<0.05， P<0.01）. Wuwei Shenqintang could normalize 17 of these compounds compared with the model group （P<0.05， P<0.01）. Fecal metabolomics results showed that compared with those in the blank group， there were 42 compounds with significant differences in the model group （P<0.05， P<0.01）. Compared with the model control group， Wuwei Shenqintang could normalize 41 of these compounds （P<0.05， P<0.01）. The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine， tyrosine， and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis， which may be related to the regulation of the "lung-intestine axis".

Objective:To explore the effectiveness of the I-PASS ABCDE structured handoff model in patients with respiratory failure in the intensive care unit (ICU) .Methods:A total of 35 nurses working in the ICU of the Affiliated Hospital of Jining Medical University were selected by convenience sampling from January 2020 to September 2021. From January to October 2020, the traditional handoff model was used (control group), while from November 2020 to September 2021, the I-PASS ABCDE structured handoff model was implemented (intervention group). The defect rate of clinical handoff, nurses' understanding of patients' conditions, handoff effectiveness, time spent on handoff, and nurse satisfaction with the handoff model were compared between the two groups.Results:The defect rate of clinical handoff in the intervention group was significantly lower than that in the control group. Scores for nurses' understanding of patients' conditions and handoff effectiveness were significantly higher in the intervention group than in the control group ( P<0.05), indicating statistical significance. Although handoff duration was longer in the intervention group than in the control group, the difference was not statistically significant ( P>0.05). Nurse satisfaction with the handoff model was significantly higher in the intervention group than in the control group ( P<0.05) . Conclusions:The application of the I-PASS ABCDE structured handoff model in ICU patients with respiratory failure can reduce handoff defects, improve handoff quality, and enhance nurses' satisfaction.

Objective:To explore the effectiveness of the I-PASS ABCDE structured handoff model in patients with respiratory failure in the intensive care unit (ICU) .Methods:A total of 35 nurses working in the ICU of the Affiliated Hospital of Jining Medical University were selected by convenience sampling from January 2020 to September 2021. From January to October 2020, the traditional handoff model was used (control group), while from November 2020 to September 2021, the I-PASS ABCDE structured handoff model was implemented (intervention group). The defect rate of clinical handoff, nurses' understanding of patients' conditions, handoff effectiveness, time spent on handoff, and nurse satisfaction with the handoff model were compared between the two groups.Results:The defect rate of clinical handoff in the intervention group was significantly lower than that in the control group. Scores for nurses' understanding of patients' conditions and handoff effectiveness were significantly higher in the intervention group than in the control group ( P<0.05), indicating statistical significance. Although handoff duration was longer in the intervention group than in the control group, the difference was not statistically significant ( P>0.05). Nurse satisfaction with the handoff model was significantly higher in the intervention group than in the control group ( P<0.05) . Conclusions:The application of the I-PASS ABCDE structured handoff model in ICU patients with respiratory failure can reduce handoff defects, improve handoff quality, and enhance nurses' satisfaction.

Objective To investigate the alteration of M1/M2 polarization of monocyte-macrophages from the peripheral blood of patients with active pulmonary tuberculosis,and the effect of Mycobacterium tuberculosis ESAT6 on the polarization of human THP-1 cells.Methods Whole blood and serum samples were collected from 14 patients with active pulmonary tuberculosis and 10 healthy controls.Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood with heparin sodium using lymphocyte fluid.The mRNA levels of HLA-DR,CD11C,CD68,CD206 and Arg-1 in PBMCs from patients with active pulmonary tuberculosis were detected by real-time quantitative PCR.The secretion of cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-4,etc.)was detected by flow cytometry.Human THP-1 cells were induced by phorbol ester(PMA)to differentiate into macrophages-like cells,which were divided into M0 group,M1 group,M2 group,and M0+ESAT6 group.After 24 hours of stimulation,the mRNA levels of HLA-DR,CD11C,CD68,CD206 and Arg-1 were detected by real-time PCR.Following stimulation with ESAT6 for 6 h,12 h and 24 h,the levels of cytokines(IL-2,IL-6,TNF-α,IL-4,etc.)in cell culture supernatant from THP-1 cells were detected by flow cytometry.Results Compared with the healthy control group,the mRNA expression levels of M1-polarized phenotypic molecules HLA-DR,CD11C and CD68 in PBMCs of the active pulmonary tuberculosis group were up-regulated(P<0.05).The mRNA expression level of M2-polar-ized phenotype molecule CD206 was decreased(P<0.05),while the expression level of Arg-1 mRNA was not statistically significant(P>0.05).Serum levels of M1-related proinflammatory cytokines IL-2,IL-6,IFN-γ and TNF-α were increased in patients with active pulmonary tuberculosis(all P<0.05),whereas decreased level of anti-inflammatory cytokine IL-4(P<0.05)were found in serum samples from patients with active pulmonary tuber-culosis.THP-1 macrophages were induced to differentiate into different phenotypes in vitro,and the HLA-DR mRNA expression level of cell M1 polarization phenotype molecule was statistically significant among all groups(F=21.83,P=0.000).Pairwise comparison results showed that expressions of HLA-DR mRNA in M1 group and M0+ESAT6 group were significantly upregulated compared with M0 group(P<0.05),there was no significant difference between the other groups(P>0.05).However,there was no significant difference in the expression of CD68 mRNA among all groups(F=2.480,P=0.135).There was no significant difference of mRNA expressions of CD206 and Arg-1 among all groups(F=1.233,P=0.3597;F=6.059,P=0.068).There were no significant differences between the M1-related pro-inflammatory cytokine IL-2 and anti-inflammatory cytokine IL-4 at different time points of cell culture(P>0.05).Compared with the M0 and ESAT6 phenotypes,the levels of pro-inflammatory cytokines IL-6 and TNF-α in the M1 phenotype group were significantly increased at 12 h and 24 h(P<0.05,P<0.05,P<0.001,P<0.001;P<0.05,P<0.05,P<0.01,P<0.01);but there was no significant difference between the other groups(P>0.05).Conclusions The ability of peripheral blood monocyte-macrophages to polarize to M1 is enhanced,while the ability to polarize to M2 is weakened in patients with active pulmonary tuberculosis.Mycobacterium tuberculosis ESAT6 can promote the polarization of macrophages to M1,which affects the activity and progression of tuberculosis.

Objective:By analyzing the cost change trend,internal structure change and main influencing factors of diabetes inpatients'hospitalization expenses,it provides empirical basis for promoting the reform of medical service prices,optimizing the internal structure of hospitalization expenses,effectively controlling hospitalization expenses,and reducing the economic burden of diabetes inpatients.Methods:Using the first page data of medical records of 13 426 diabetes inpatients in the target hospital from 2017 to 2021,it analyzes the structural change of diabetes inpatients'hospitalization expenses by using structural change degree and grey correlation degree methods,and analyzes the influencing factors of hospitalization expenses by using linear regression and BP neural network model.Results:Drug expenses and medical technology expenses are the top two in the proportion of total hospitalization expenses of discharged patients with diabetes,and they account for a large proportion in the total hospitalization expenses.The results of structural change and grey correlation show that drug expenses and medical technology expenses are these two factors that cause changes in the total hospitalization cost structure and have a high correlation with the total hospitalization cost,with a cumulative contribution rate of 90.50％.According to the results of linear regression and neural network model,the length of stay is the most important factor affecting the total cost of hospitalization of diabetes patients,followed by the number of operations/procedures and diagnoses.Conclusion:The internal composition of hospitalization expenses for diabetes patients is unreasonable.The proportion of drug expenses and medical technology expenses is too high.The proportion of medical and nursing expenses reflecting the technical labor value of medical personnel is relatively low.The structure of medical income needs to be further optimized.The length of stay is the most critical factor affecting the hospitalization expenses of diabetes patients.Reasonable control of the length of stay can effectively control the unreasonable growth of medical expenses and reduce the economic burden of diabetes patients.

OBJECTIVE To explore and establish a long-term mechanism for rational control of intravenous fluids in hospitals. METHODS On the basis of the establishment of rules and regulations， through the exploration and implementation of the core technical strategy of “six-step method”， a new mode of intravenous infusion control was established. The contents of the “six-step method” were as follows： the first step was to sort out the diseases that did not require intravenous infusion； the second step was to sort out the alternative drugs/dosage forms； the third step was to sort out the alternative routes of infusion； the fourth step was to develop drug specifications； the fifth step was to explore the personalized medication needs of clinical departments； the sixth step was to develop a department-specific integrated infusion regimen. The utilization rate of intravenous fluids in inpatients and the average daily amount of intravenous fluids per bed in inpatients were used as the main indicators to evaluate the control effect. RESULTS The comparison of the average values of three months before and after the implementation of the “six-step” management mode in the department of thoracic surgery of our hospital showed that after management and control， the average utilization rate of intravenous fluids in inpatients decreased by 1.74%， the average daily use of intravenous fluids in inpatients per bed decreased by 0.30 bags/bottle， and the per capita use of infusion drugs under key control gradually decreased. CONCLUSIONS The “six-step” management mode can reduce the utilization rate of intravenous fluids in inpatients， and this management mode is practical and feasible.