Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To analyze the influence of forming direction on the surface characteristics,elastic modulus,bending strength and fracture toughness of printed parts and the relationship between forming direction and force direction,and to provide scientific basis and guidance for the clinical applica-tion of oral denture base resin materials.Methods:The 3D printing technology was used to print denture base resin samples.The shape and size of the samples referred to the current standard for testing conven-tional denture base materials.The samples used for physical performance testing were cylindrical(with a diameter of 15 mm and a thickness of 1 mm)and printed at different angles along the Z axis(0°,45°,90°).Scanning electron microscope was used to observe the microscopic topography of the different sam-ples.The color stability of different samples was observed by color stabilizer.The surface roughness of the samples was analyzed by using surface roughness tester.The Vickers hardness was measured to ana-lyze the hardness of the samples.The samples used for mechanical performance testing were rectangular(elastic modulus and bending strength:A length of 64 mm,a width of 10 mm,and a height of 3.3 mm;fracture toughness:A length of 39 mm,a width of 8 mm,and a height of 4 mm),divided into two groups:W group and H group.The W group was printed from the bottom up along the Z axis with the length × width as the bottom surface parallel to the X,Y axis plane,while the H group printed from the bottom up along the Z axis with the length × height as the bottom surface parallel to the X,Y axis plane.The forming angles of both groups were equally divided into 0°,45°,and 90°.The elastic modulus,bending strength and fracture toughness of different samples were studied through universal mechanical testing machine.SPSS 22.0 software was used for statistical analysis.Results:The microscopic topogra-phy and roughness of different samples were closely related to the printing direction,with significant differences between the 0°,45°,and 90° specimens.The 0° specimens had the smoothest surface(roughness＜1 μm).The surface of the 45 ° specimen was the roughest(roughness＞3 μm).The microhardness of the 0° sample was the best[(196.13±0.20)MPa],with a significant difference com-pared with the 90° sample[(186.62±4.81)MPa,P＜0.05].The mechanical properties of different samples were also closely related to the printing direction.The elastic modulus,bending strength,and fracture toughness of the 45° samples in the W group were the highest compared with the other groups.The results of elastic modulus showed that in the H group,the 45° specimens had the highest elastic mo-dulus,which was significantly different from the 0° and 90° specimens(P＜0.05).The elastic modulus of 0° and 45° specimens in the W group were higher than those in 90° specimens(P＜0.05).The bending strength results showed that there was no significant difference between the specimens from dif-ferent angles in the H group.The bending strength of the 90° specimens in the W group was the smallest,and there was a significant difference between 90° and the 0° and 45° specimens(P＜0.05);And the bendind strength of the 0° and 45° specimens in the W group was significantly higher than that of the 0° and 45° specimens in the H group(P＜0.05).The fracture toughness results showed that the fracture toughness of the H group specimens was lower than 1.9 MPa m1/2,which was specified in the denture base standard.The 45° samples in the W group were the highest,with significant differences compared with the 0° and 90° samples(P＜0.05).And the 90° samples of the W group specimens were lower than 1.9 MPa m1/2.And the fracture toughness of the 45° specimen in the W group was significantly higher than that of all the specimens in the H group(P＜0.05).Conclusion:The 0° samples had rela-tively better physical properties.The 45° samples had the best mechanical properties.But the fracture toughness of specimens(H group and 90° samples of W group)did not yet meet clinical requirements.That indicated that the characteristics of the 3D printing denture base resin were affected by the printing direction.Only when the performance of the printed samples in all directions met the minimum require-ments of the standard,they could be used in clinical practice.

Objective To investigate the plasma level of interleukin-31(IL-31)in patients with pulmonary arterial hypertension(PAH)and its clinical relevance.Methods The patients who were diagnosed as PAH in Zhongshan Hospital,Fudan University from January 1,2021 to December 30,2023(PAH group)and the healthy people in the same period(control group)were selected.The clinical data and follow-up records were collected.Plasma levels of IL-31,IL-1β,IL-6,IL-10,IL-12p70,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation test was used to evaluate the correlations between IL-31 and right cardiac catheterization parameters,echocardiography parameters and blood indices in patients with PAH.Cox proportional hazard model was used to analyze the prognostic factors of patients in PAH group.Results A total of 50 patients with PAH and 22 healthy controls were included.There was no significant difference in age,gender,body mass index and left ventricular ejection fraction between the two groups.Compared with the control group,the plasma level of IL-31 in the PAH group was significantly higher(168.82[149.14,177.26]pg/mL vs 152.76[145.58,159.41]pg/mL,P=0.001).Pearson correlation test showed that the plasma level of IL-31 in PAH patient was positively correlated with mean pulmonary artery pressure(r=0.652,P＜0.001)and pulmonary vascular resistance(r=0.651,P＜0.001),but was negatively correlated with tricuspid annular plane systolic excursion(r=-0.496,P＜0.001).Cox proportional hazard model showed that higher plasma level of IL-31 was an independent predictor of readmission for heart failure/all-cause mortality in patients with PAH(HR=1.130,95％CI 1.052-1.214,P=0.001).Conclusions Plasma level of IL-31 may be significantly increased in patients with PAH and be positively correlated with the severity of PAH,and elevated level of IL-31 is predictive of poor prognosis in PAH patients.

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

Objective:To explore the application effect of the modified presentation assimilation discussion combined with heuristic clinical medicine teaching in training of extracorporeal membrane oxygenation specialist nurses.Methods:The convenient sampling method was used to select 62 nurses who participated in training of extracorporeal membrane oxygenation specialist nurses in the Second Affiliated Hospital of Zhengzhou University from January to June 2023 as the research objects. A total of 30 nurses who participated in the 25th training session from January to March 2023 were selected as the control group, and 32 nurses who participated in the 26th training session from April to June 2023 were selected as the observation group. The control group received conventional training method, while the observation group received modified presentation assimilation discussion combined with heuristic clinical medicine teaching. The theoretical knowledge and operational skills of nurses, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction were compared between the two groups after training.Results:After training, the scores of theoretical knowledge and operational skills, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified presentation assimilation discussion combined with heuristic clinical medicine teaching can improve the theoretical knowledge and operational skills of extracorporeal membrane oxygenation specialist nurses, and the nurses' training satisfaction is higher.

AIM: To investigate the absorption of helicid in different segments of intestine based on rat everted intestine sac model. METHODS: To establish a high-performance liquid chromatography method for simultaneous determination of helicid and its metabolite. Krebs-ringer solution containing helicid was added to everted intestine sacs of different segments (duodenum, Jejunum, ileum and colon). Drug concentration in sacs was determined at different time points (5, 10, 15, 30, 45, 60, 75, 90 min). Adsorptions of helicid in four intestinal segments were compared. RESULTS: This high-performance liquid chromatography was successfully applied to the simultaneous determination of helicid and its metabolite. Absorption of helicid was rapid and time-dependent. The absorption and metabolism of helicid in duodenum segment were higher than these in other segments. CONCLUSION: The duodenum segment is the main site of segmental absorption and metabolism of helicid. This is the first report on intestinal segment metabolism of helicid.

Myeloma is a malignancy associated with significant immune dysfunction imparted by both the disease itself as well as many of the immunosuppressive therapies that have been used in the past.The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signalling axes.This review summarized the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma.Finally,several current challenges and possible future direction of immune checkpoint blockade in myeloma will be reviewed.

Objective To investigate the effect and mechanism of chitosan on vascular smooth muscle cell proliferation of uremia patients with arteriovenous fistula.Methods Primarily culturing the VSMCs of uremia patients with arteriovenous fistula and patients without uremia by explants adherent method,and taking the second generation.VSMCs from patients without uremia cultured with 20％ FBS medium were non-uremia group,VSMCs of uremia patients cultured with 20％ FBS medium were uremia group,VSMCs of uremia patients with 100 pg/ml chitosan were uremia+ chitosan group.The expression of α-SMA was detected by immunohistochemistry.The changes of migration and invasion of VSMCs were detected by scratches and transwell migration assays.The mRNA expressions of TLR4 and PCNA were measured by real-time PCR.VSMCs of uremia patients with arteriovenous fistula were intervened with different doses of chitosan (0,100 and 500 μg/ml),and the protein expressions of TLR4,MyD88 and NF-κB were detected by Western blotting.Results Compared with those in non-uremia group,in uremia group and uremia+chitosan group α-SMA was upregulated,migration and invasion of VSMCs were enhanced,and mRNA expressions of TLR4 and PCNA were increased (all P ＜ 0.05).Compared with those in uremia group,the level of α-SMA was significantly decreased,the ability of migration and invasion of VSMCs were decreased,and the mRNA expressions of TLR4 and PCNA were decreased (all P ＜ 0.05).TLR4,MyD88 and NF-κB protein expressions were reduced in concentration-dependent manner by 100 and 500 μg/ml chitosan.Conclusions (1) In vitro,chitosan decreases the ability of migration and invasion of VSMCs of uremia patients with arteriovenous fistula.(2) Chitosan inhibits the proliferation of VSMCs,which may be relevant in the decreased expressions of TLR4,MyD88 and NF-κB.

Objective To analyze the differences in the PDCD1 gene copy number of hepatocellular carcinoma and paracancerous tissues in patients with hepatocellular carcinoma (HCC) after HBV infection.Methods Analysis PDCD1 gene copy number of 27 paraffin embedded specimens of hepatocellular carcinoma tissues and para carcinoma tissues of patients with hepatocellular carcinoma after resection by Taqman real-time PCR.Results The gene copy number of PDCD1 of hepatocellular carcinoma tissue and paracancerous tissue had no significant difference (P ＞ 0.05) ; the gene copy number of PDCD1 and preoperative AFP levels of hepatocellular carcinoma and paracancerous tissues had no significant correlation (P ＞ 0.05).Gene copy number of PDCD1 of hepatocellular carcinoma and paracancerous tissues had no significant correlation with tissue tumor malignant degree (P ＞ 0.05).Conclusions PD-1 plays a role in the escape response of tumor immunity,but the PDCD1 gene copy number variation of hepatocellular carcinoma and paracancerous tissues is not a factor in carcinogenesis and development of hepatocellular carcinoma.

AIM: To investigate the downstream genes of the transcriptional factor Pax-8 related to cardiopathy. METHODS: The total RNA derived from the heart of Pax-8 KO~(-/-) and Pax-8 KO~(+/-) mice was extracted. Mouse genome DNA microarray containing 31 802 mouse oligonucleotides probes was used to investigate the differential expression between the Pax-8 KO~(-/-) and the Pax-8 KO~(+/-) mice hearts. The candidate genes were confirmed by RT-PCR and real time RT-PCR assay. RESULTS: Microarray results showed that, compared to the Pax-8 KO~(+/-) mice, 25 genes were down-regulated and 17 were up-regulated in the Pax-8 KO~(-/-) mice, concerning metabolize enzymes, cell signal conducting and nuclear transcript factors and so on. Bcl2-like 14 (Bcl2l14) was proved to be up-regulated by RT-PCR. Real time RT-PCR results revealed that Bcl2l14 in the Pax-8 KO~(-/-) mice was 2.07 and 2.23 fold as much as that in the Pax-8 KO~(+/-) and the Pax-8KO~(+/+) mice (P<0.01). CONCLUSION: The Bcl2l14 gene is one of the downstream genes of Pax-8 and probably plays an important role in the mechanism of ventricular septum defect.