Objective: To explore the effects of a zerotime exercise (ZTEx) intervention on physical activity levels and sedentary behavior among college students, providing evidence for improving physical activity and reducing sedentary habits. Methods: In September 2023, 45 sedentary college students from a university in Fuzhou were recruited and randomly assigned to either the ZTEx group (23 students) or the control group (22 students) according to a random number table method. ZTEx group received two ZTEx focus group meetings for 3 months, while the control group received safety and health education. The International Physical Activity Questionnaire and a threeaxis accelerometer were used to evaluate the sedentary and physical activity levels of college students. At the same time, evaluations related to physical health and psychological questionnaires were completed. Mixed effects analysis of variance and nonparametric tests were used to statistically analyze the physical health, psychological questionnaire, and sedentary and physical activity data of the college students. Results: Postintervention, the ZTEx group showed significant improvements in the duration of lowintensity physical activity [pretest(1 492.78±369.50)min; posttest(1 918.93±354.63)min] and the number of sedentary interruptions [pretest(45.26±13.69)times; posttest(73.78±16.74)times]; grip strength [pretest(28.77±9.23)kg; posttest(31.78±8.00)kg]; sitting up continuously for 30 seconds [pretest(22.52±4.90)times; posttest(26.96±4.87)times]; general selfefficacy [pretest(26.52±4.14)points; posttest(32.96±5.24)points]; body composition summary [pretest(66.44±4.83)points; posttest(72.62±4.88)points]; and psychological composition summary [pretest(61.21±9.88)points; posttest(63.98±9.57)points], while reducing sedentary time [pretest(3 694.28±687.56)min; posttest(2 865.90±493.81)min] in the past 7 days, the differences were statistically significant(P<0.05). The control group exhibited no significant changes(P>0.05). Conclusion ZTEx effectively improve the lowintensity physical activity, increases sedentary breaks, and reduces prolonged sitting among college students, fostering healthier habits and improving physical/mental wellbeing.

Objective To analyze the changing prevalence and resistance profiles of multiple drug-resistant(MDR)bacteria in Minhang Hospital of Fudan University before and after the onset of COVID-19 pandemic.Methods The resistance profiles of 6 bacterial species were compared before(2017-2019)and after(2020-2022)the onset of COVID-19 pandemic.WHONET 5.6 software was used to statistically analyze the data of antimicrobial susceptibility testing.Results After the onset of COVID-19(2020-2022),the prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKP)was significantly higher than that in the pre-pandemic period(2017-2019)(40.1％vs 27.9％,P＜0.01),while the prevalence of carbapenem-resistant Escherichia coli(CREC)decreased significantly(1.9％vs 3.1％,P＜0.05).The prevalences of carbapenem-resistant Acinetobacter baumannii(CRAB),carbapenem-resistant Pseudomonas aeruginosa(CRPA),methicillin-resistant Staphylococcus aureus(MRSA),and vancomycin-resistant Enterococcus(VRE)did not show significant difference before and after the onset of COVID-19 pandemic.MDR isolates were mainly isolated from respiratory tract samples either before or after COVID-19 pandemic(78.4％vs 78.5％).The prevalence of MDR in the intensive care unit(ICU)was significantly higher during the period from 2020 to 2022 compared to the pre-pandemic period(53.1％vs 35.5％,P＜0.01).The resistance rate of MRSA to methoprim-sulfamethoxazole decreased from 15.7％during 2017-2019 to 3.5％during 2020-2022(P＜0.01).Compared to the pre-pandemic period,the E.faecalis strains showed lower resistance rates to penicillin G,ampicillin,and levofloxacin during 2020-2022.The resistance rate of E.faecium to high-level gentamicin decreased significantly from 50.1％during 2017-2019 to 39.2％during 2020-2022(P＜0.01).The resistance rate of E.coli to imipenem decreased from 2.7％to 1.2％(P＜0.01),while A.baumannii and P.aeruginosa strains showed stable resistance rates to carbapenems(P＞0.05).Conclusions After the onset of COVID-19 pandemic,the prevalence of CREC decreased significantly.The prevalences of CRAB,CRPA,MRSA,and VRE also showed a decreasing trend.However,the prevalence and resistance rates of CRKP significantly increased.It is necessary to strengthen hospital infection control measures to curb the spread of MDR bacteria.

Objective:To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma(MM).Methods:The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively,including 43 newly diagnosed patients and 17 patients with recurrence and progression.All patients were treated with ixazomib combined with thalidomide and dexamethasone,and completed 2 to 7 treatment cycles.Results:The overall response rate(ORR)of all patients was 98.3％.Among them,53 patients completed 4 treatment cycles,and the ORR was 86.8％.Seventeen patients completed the whole treatment cycle,with curative effect reaching 88.2％achieving very good partial response and above,and 52.9％achieving complete response and above.Albumin and β2-microglobulin of all patients had been improved rapidly after treatment.The deadline was August 31,2022.The median follow-up time was 14(3-24)months,and overall survival(OS)rate was 86.67％.The OS rate of patients with recurrence and progression was significantly lower than that of newly diagnosed patients(P＜0.05).The most common adverse reaction of hematology was lymphopenia(53.3％),followed by anemia(33.3％).The most common non-hematological adverse reaction was fatigue(68.33％),followed by peripheral neuropathy(31.67％).Conclusion:Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM,with good short-term efficacy,survival and safety.However,its long-term efficacy needs further observation.

Objective:To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism.Methods:Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting.Results:Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). Conclusion:QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Objective:To explore the value of 18F-fibroblast activation protein inhibitor (FAPI) PET/CT in the assessment of early-stage graft fibrosis (S1-S2) after liver transplantation (LT). Methods:From November 2021 to April 2022, 17 adult liver transplant recipients (12 males and 5 females; age (52.6±7.9) years) in the Affiliated Hospital of Qingdao University were enrolled retrospectively in this study. All 17 patients received laboratory examinations, FibroScan, 18F-FAPI PET/CT and liver biopsy. According to the Scheuer scoring system, hepatic tissue was divided into no fibrosis (S0) and early fibrosis (S1-S2). Independent-sample t test was used to compare SUV max between two groups, and Mann-Whitney U test was used to compare liver stiffness measurement (LSM). ROC curve analysis was used to evaluate the diagnostic efficacy of LSM and SUV max in the early fibrosis of liver grafts. Delong test was used to compare the difference of AUCs. Results:Among 17 adult LT recipients, 11 were in stage S0, 5 were in stage S1, and 1 was in stage S2. There were significant differences in LSM and SUV max between no fibrosis group and early fibrosis group (LSM: 5.4(4.7, 6.6) vs 12.9(5.6, 19.9) kPa, z=-2.01, P=0.044; SUV max: 1.7±0.8 vs 3.9±1.6, t=-3.14, P=0.019). The threshold value of LSM in predicting early-stage graft fibrosis was 8.2 kPa and the AUC was 0.80 (95% CI: 0.54-0.95), which was 2.0 and 0.92 (95% CI: 0.78-1.00) for SUV max respectively. There was no significant difference in AUC between the two tools ( z=0.80, P=0.421). Conclusion:18F-FAPI PET/CT can precisely evaluate the early fibrosis of allografts, with the similar diagnostic efficacy with FibroScan (LSM), which is expected to be a new non-invasive diagnostic tool for predicting the early-stage of graft liver fibrosis.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective:To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells.Methods:The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects.Results:① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138 + cells with a binding affinity constant (K D) of 6.011×10 -9 mol/L and showed no significant binding activity with CD138 - cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138 + myeloma cell line H929, whereas CD138 - cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138 + cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138 - cells. Conclusion:This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.

Objective To design an anti-inversion performance evaluation system for ankle braces and validate its performance.Methods The system was composed of a simulation system,an inversion angle acquisition system,a lateral tension acquisition system for ankle joint and a data collection and procession system.The simulation platform made of aluminum alloy consisted of a standing platform and a landing pad,and the landing pad was made up of a platform and a slope for landing;the inversion angle acquisition system included markers,an image acquisition device and a fill light.The lateral tension acquisition system involved in a tension sensor,a detection sensor and an elastic cloth for fixation.The data collection and procession system comprised of a computer or smartphone,iXControl software,iXViewer software and a cell phone App that received real-time data from the lateral ankle tension acquisition device.The system developed underwent performance validation when applied to evaluating anti-inversion performance of volunteers without or with flexible or new braces.The traditional EMG testing method was used for EMG data acquisition for volunteers without or with flexible or new braces,and the consistency was explored between the testing results by the traditional method and the system.Results The system developed could evaluate the anti-inversion performance of ankle braces by simulating the process of ankle inversion during human high-altitude landing,and the results had high consistency with those by traditional EMG testing methods.Conclusion The system developed with simple structure and easy operation evaluates the anti-inversion performance of ankle braces.[Chinese Medical Equipment Journal,2024,45(11):21-26]

Objective:To systematically evaluate the efficacy and safety of Suhuang Zhike Capsules in treating chronic obstructive pulmonary disease(COPD)and to analyze the multi-target and multi-pathway intervention mechanisms of Suhuang Zhike Capsules in treating COPD using network pharmacology and molecular docking technology.Methods:Based on meta-analysis,the clinical total effective rate and adverse reactions of Suhuang Zhike Capsules in treating COPD were evaluated.The effective components and action targets of Suhuang Zhike Capsules were preliminarily predicted through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and GeneCards database,respectively,and the target information was standardized.COPD targets were selected through various databases.Suhuang Zhike Capsules targets and COPD targets were integrated to obtain the key targets for treating COPD.A protein-protein interaction(PPI)network was constructed to identify core targets,and GO and KEGG enrichment analyses were performed for intersection targets.The key active components of Suhuang Zhike capsule and core targets of COPD were verified by molecular docking.Results:Results of meta-analysis showed that compared with conventional treatment,combined with Suhuang Zhike Capsules significantly improved the clinical total effective rate(OR=4.26,95%CI:3.20-5.68,P＜0.01).There was no statistically significant difference between the two groups in the incidence of adverse reactions(P＞0.05).The network pharmacology results showed 90 active compounds,141 COPD-related targets,and 103 related pathways.Molecular docking results indicated that the core components of Suhuang Zhike Capsules,such as luteolin,quercetin,and kaempferol,were successfully docked with core targets of COPD,including epidermal growth factor receptor(EGFR),serine/threonine kinase 1(AKT1),and matrix metalloproteinase 9(MMP9),with all binding energies＜-5 kcal/mol,indicating good binding activity.Conclusions:Conventional treatment combined with Suhuang Zhike Capsules can improve clinical efficacy and has good safety in treating COPD.Suhuang Zhike Capsules may be involved in the treatment of COPD through multiple-target and multiple-pathway.This study provides bioinformatics support and safety evaluation for the clinical application of Suhuang Zhike Capsules in treating COPD and provides new insights for further research.

Pyroptosis is a newly discovered kind of cell death modality that, due to its association with innate immunity, plays a crucial role in cytolysis and inflammatory cytokine release during host defense against infection. In recent years, studies have shown that pyroptosis plays an important role in the occurrence and development of liver diseases. This article introduces and elaborates on the most recent research progress on pyroptosis in liver diseases based on the morphological features, molecular and pathophysiological mechanisms.