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.

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Objective:To investigate the application effect of Press-Z-track-Turn (PZT) intramuscular injection on the extravasation, local reaction, local pain after injection and patient satisfaction after Fulvestrant injection.Methods:Used a self-controlled study, 63 patients who underwent bilateral intramuscular injection of Fluvastatin in the outpatient injection room of Tianjin Medical University Cancer Hospital from August to October 2022 were conveniently selected. The observation time was two treatment cycles after inclusion in this study. Before the injection of the first treatment cycle, a coin toss was used to randomly decide to use traditional intramuscular injection and PZT intramuscular injection method for injection and record. After 28 days, another injection method was used, with a total of 126 injections per injection method. Observed the extravasation of drug solution and local reactions at the injection site within 7 days after injection using two injection methods, as well as the pain and satisfaction of patients within 7 days after injection.Results:The extravasation rate of drug solution for the PZT intramuscular injection was 1.59% (2/126), which was lower than 7.14% (9/126) for the traditional intramuscular injection, and the difference was statistically significant ( χ2=4.66, P<0.05); the incidence of mild and moderate local reactions for the PZT intramuscular injection was 3.97% (5/126) and 1.59% (2/126), respectively, lower than that for the traditional intramuscular injection 11.11% (14/126) and 5.56% (7/126), and the difference was statistically significant ( χ2=8.26, P<0.05); the pain score of the PZT intramuscular injection was (2.08 ± 0.85) points, lower than that of the traditional intramuscular injection (5.03 ± 1.06) points, and the satisfaction score of the PZT intramuscular injection was (23.68 ± 1.64) points, higher than that of the traditional intramuscular injection (20.10 ± 2.58) points. The difference was statistically significant ( t=-17.24, 9.16, both P<0.01). Conclusions:PZT intramuscular injection can effectively reduce the overflow rate, the incidence of grade 1 and 2 local reactions and the degree of pain of patients, and improve patient satisfaction, which is worthy of clinical application.

Objective Streptococcus sanguis is a possible candidate bacterium for the caries replacement therapy, which has no advantages in the acidic environment.The aim of the study was to construct acid-resistant strains of Streptococcus sanguis, determine its acid tolerance, and explore the mechanism of its antagonism against Sterptococcus mutans.Methods By gradually reducing the pH value of the medium, we constructed acid-resistant strains of Streptococcus sanguis, observed their growth and measured their acid tolerance according to their survival rate against lethal pH.We evaluated the competitive relationship between Streptococcus sanguis and Streptococcus mutans by plate experiment and detected the changes of related acid resistance genes by real-time quantitative PCR.Results The growth of Streptococcus sanguis and its acid-resistant strains were limited by the pH value, and that of Streptococcus sanguis was better in either acidic or normal environment.The lethal pH value of Streptococcus sanguis was 3.6, that of its acid-resistant strains was 2.3, and the survival rate of the acid-resistant strains was 66.59% in the pH 3.6 environment.In comparison, the lethal pH value of Streptococcus mutans was 2.5, that of its acid-resistant strains was 2.1, and the survival rate of the acid-resistant strains was 2.55% in the pH 2.5 environment.In the presence of chloramphenicol, the acid-resistant strains could not survive in the original lethal pH.In the sub-lethal pH environment, the expressions of the acid resistance-related genes Groel and Dnak in the acid-resistant strains were significantly up-regulated as compared with those in the original Streptococcus sanguis (P<0.05).Conclusion Streptococcus sanguis has an acid adaptability and can enhance acid resistance in the sub-lethal pH environment.Acid-resistant Streptococcus sanguis in the replacement therapy may provide some new ideas for the treatment of dental caries.

Objective Studies have shown that low concentrations of nicotine can promote neovascularization and promote wound healing.This article aimed to investigate the influence of low concentration collagen membrane slow-release system on the hard palate trauma of rats.Methods Using poly(lactic acid-co-glycolic acid) (PLGA) copolymer as carrier materials, low concentration nicotine sustained-release particles were prepared by emulsion evaporation method (w/o/w), using collagen membrane as the brace and establish a low concentration collagen membrane system.48 Wistar rats were divided into experimental group and blank group, 3 mm diameter circular wound was made in the forepart palate.Low concentration of nicotine collagen membrane sustained-release particle system and blank collagen membrane (control) were sutured on the wound with 6-0 absorbable thread.Then, observed the wound healing of 0, 3, 7, 10 days and compared the healing differences between each groups.Results Under the electron microscope, the nicotine sustained-release particles were circular, similar size with rough surface, the average diameter were 3.0±0.2μm, the encapsulation efficiency and drug loading rate was 50.2% and 4.12% respectively.In vitro, nicotine sustained-release particles released much more nicotine on the first day, less on the second day, tends to stable and fluctuate within a certain range from the third day on, and declined sharply after about 10 days, nicotine concentration from 3rd to 10th day was fluctuate within 10-5-10-4mol/L.Postoperative wound healing, no significant difference in 3 days(P>0.05), after 7 days, the wound healing of experimental group significantly greater compared with the control (P=0.015).The wound was healed in 10 days after operative, there was no significant difference between two groups(P>0.05).The epithelial proliferation in the experimental group was significantly greater than that in the blank group, there were many fibroblasts, inflammatory cells and new capillaries, the epithelial process is short, the submucosa is loose, and a large number of collagen fibers are produced.The lamina propria is closely connected with the periosteum, and the wound is healed Conclusion Low concentration of nicotine sustained-release particles collagen membrane system may promote wound healing in the hard palate mucosa of rats.

Progressing vasopressor-refractory hypotension is a major contributor to the high mortality of septic shock.The effect of corticosteroids on peripheral vascular circulation recovery and immune modulation is crucial to the survival of patients with septic shock .However, despite more than fifty years of animal experiments and human trials, the role of corticosteroid therapy in septic shock , its proper applications including dosage, duration and withdrawal remain uncertain and controversial .This paper reviews the development of research , the mechanism, application, and the future direction of low-dose glucocorticoids in the treatment of septic shock .

Objective Antimicrobial peptides are the focus of recent research in oral microbiology .This study aimed to eval-uate the activity of a novel antimicrobial peptide pm 11 against oral microorganisms and its action mechanisms . Methods We ana-lyzed the effect of pm11 on oral microorganisms and determined its antimicrobial activity in the saliva environment by measuring its min -imal inhibitory concentration (MIC), minimal bactericide concentration (MBC), and bactericidal kinetics.We observed its bacteri-cidal activity on the biofilms of streptococcus mutans by confocal laser scanning microscopy (CLSM) and the structural changes in the bacterial membrane by scanning electron microscopy (SEM). Results The antimicrobial activity of pm11 varied greatly against dif-ferent oral microorganisms , with its MIC values ranging from 2 μg/mL to 256 μg/mL and its MBC values from 2 μg/mL to >256μg/mL.The bactericidal kinetics showed a decreasing survival rate of bacteria with the lengthening of the intervention time .The inhib-itory-zone diameters exhibited no significant indifference between the water solution and the sterile saliva solution .CLSM revealed an increased number of dead bacteria in the pm 11-treated biofilms , while SEM manifested obvious changes in the shape of the bacteria membrane treated with pm11. Conclusion Our findings suggest that pm11 has a broad spectrum of antimicrobial activities on oral mi-croorganisms and a potential value of clinical application .

[Abstract ] Objective More and more researches demonstrate that epithelial-mesenchymal transition(EMT) is highly rele-vant to cancer metastasis , tissue fibrosis and skin wound healing , but its role in the wound healing of oral mucosa still needs further ex-ploration.This study was designed to discuss the effects of EMT on the wound healing of lingual mucous membrane in rats . Methods A 3mm-diameter circular defect was made on the mucosa of lingual dorsum in 8-week-old Wistar rats.The rats were put to death at day 0, 1, 2, 3, 4 and 8 after operation.We observed tissue healing process by HE staining and used immunohistochemical fluorescence to detect the expressions of EMT-related protein E-cadherin(E-cad), Vimentin and Fibroblast specific proteins (FSP1) in lingual mucous membrane during wound healing . Results The expressions of E-cad at the edge of the wound in the lingual mucous membrane of rats at day 2 and 4 after operation were less than those at day 0 and 1 after operation , while interstitial cell specific protein Vimentin and FSP1 were positively expressed in the epidermal basal layer .The wound of lingual mucous membrane healed completely at day 8 after operation , and E-cad expression was close to that at day 0 after operation .A small amount of Vimentin and FSP 1 expressed in the epi-thelial basal layer . Conclusion E-cad, Vimentin, FSP1 are involved in the wound healing process of lingual mucous membrane . During the wound healing in the tongue mucous membrane of rats , some epithelial cells gain the feature of mesenchymal cells in the process of migration to wound centre .EMT has played an important role during wound healing of lingual mucous membrane in rats .

BACKGROUND:Low concentration of nicotine promotes the angiogenesis and facilitates the healing of skin wounds. However, the role of low concentration of nicotine on the repair of maxil ofacial soft tissue trauma especial y oral mucosa stil remains unclear
OBJECTIVE:To evaluate the effect of low concentration of nicotine on mucosa defect repair of rat hard palate.
METHODS:A circular soft tissue defect at 3 mm diameter was produced in the centre of hard palate of 65 Wistar rats. After the operation, animals were randomly divided into low concentration of nicotine with gel group, gel group and control group. Rats were sacrificed at 3, 7, 10 and 14 days post-surgery. The wound healing was detected with hematoxylin-eosin staining and the difference of wound healing in different groups was compared with gross observation and image measurement.
RESULTS AND CONCLUSION:There was no significant difference in the wound healing in different groups on day 3 post-surgery. On days 7 and 10, the group of low concentrations of nicotine with gel was faster than gel group and control group (P<0.05);the wounds were completely healed on day 14, with no significant difference among the groups. Low concentrations of nicotine may promote the mucosa defects repair of rat hard palate.

Background Dry eye is increasing gradually recently,but its etiology and manifestation are very diverse.Studies showed that menopause of adult females was one of the risk factors of dry eye.In addition,some inflammatory factors also participate in the pathogenesis and development.But the study on the relationship of sex hormone with inflammation and ocular surface damage is still below understanding.Objective This study was to investigate the expressing changes of interleukin (IL) and tumor necrosis factor-α (TNF-α) in conjunctiva and the manifestation of ocular surface in ovariectomized rat model.Methods Twenty clear female SD rats were randomized into the ovariectomized group and the sham operative group according to randomized number table.Ovariectomy was performed in the ovariectomized group,and abdominal myotomy without ovariectomy was performed in the sham operative group.Serum estrogen and androgen levels were detected by radiation immunoassay 3 months after operation.Schirmer Ⅰ test (S Ⅰ t) and corneal fluorescence staining were carried out in the rats before operation and 1 month,2 and 3 months after operation.The morphology of conjunctival epithelial cells was examined by hematoxylin & eosin staining at the 3rd month after operation.The expressions of IL-17A,IL-1 β,IL-6 and TNF-α in conjunctiva were semi-quantitative analyzed by immunohistochemistry and Western blot.The use and care of the animals complied with State Science and Technology Commission Regulations for the Administration of Affair Concerning Experimental Animals.Results Serum estrogen levels were (23.53 ± 1.65) pg/L and (47.89 ± 1.05) pg/L 3 months after surgery in the ovariectomized group and the sham operative group,respectively; the serum androgen levels were (1.84±0.09) ng/L and (2.47±0.12)ng/L in the ovariectomized group and the sham operative group,respectively,showing a significant decline of serum estrogen and androgen levels in the ovariectomized group compared with the sham operative group (t=-35.37,-12.13,both at P＜0.01).No significant differences were seen in S Ⅰ t between the two groups among various time points (Fgroup =0.38,P =0.55 ; Ftime =0.13,P =0.72 ; Finteraction =0.39,P =0.76).No obvious fluorescence staining was seen in the cornea of both the ovariectomized group and the sham operative group.The histopathological examination showed that the layers of rat conjunctival epithelial cells increased with the disordered arrangement in the ovariectomized group.Immunochemistry showed that the expressions of IL-17A,IL-1β,IL-6 and TNF-α (A values) were significantly higher in the ovariectomized group than those in the sham operative group (IL-17A:t=8.22,P＜0.01 ;IL-1β:t=16.43,P＜0.01 ;IL-6:t=13.44,P＜0.01 ;TNF-α:t=16.26,P＜0.01).Western blot assay showed the similar results (IL-17A:t=19.41,P＜0.01 ;IL-1β:t=12.63,P＜0.01 ;IL-6:t=17.17,P＜0.01 ;TNF-α:t=15.19,P＜0.01).Conclusions Serum estrogen and androgen levels drop obviously,and there is an up-regulation of IL and TNF-α expression in conjunctiva tissue in the ovariectromized SD rats.However,no obvious dry eye-related sign occurs.