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.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective:To investigate the clinical efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC (albumin-bound paclitaxel + carboplatin) regimen in the treatment of advanced squamous non-small cell lung cancer (NSCLC) with driver gene negative and programmed death-1 receptor ligand 1 (PD-L1) expression positive.Methods:A prospective case-control study was performed. A total of 84 advanced squamous NSCLC patients with driver gene negative and PD-L1 expression positive in Hebei Seventh People's Hospital from January 2020 to December 2022 were collected, and all patients were divided into the observation group and the control group according to the random number table method, with 42 cases in each group. The control group was given the treatment of sintilimab combined with nab-PC regimen, and the observation group was given deep hyperthermia on the basis of the control group. After 4 consecutive cycles of treatment, the short-term efficacy of the two groups was compared. The levels of serum tumor markers [carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), cytokeratin fragment 19 (CYFR21-1)], and the positive expression rates of immunohistochemistry markers [p40, p63, and cytokeratin 5/6 (CK5/6)] before and after treatment were compared between two groups. Functional Assessment of Cancer Therapy-Lung cancer module (FACT-L) scores, the adverse reactions and the long-term survival of the two groups were compared.Results:There were 26 males and 16 females in the observation group, and the age was (59±11) years; there were 22 males and 15 females in the control group, and the age was (58±11) years. The objective remission rate and the disease control rate were 71.43% (30/42), 90.48% (38/42), respectively in the observation group, and 50.00% (21/42), 80.95% (34/42), respectively in the control group; the objective remission rate in the observation group was higher than that in the control group, and the difference was statistically significant ( χ2 = 4.04, P = 0.044); and there was no statistically significant difference in the disease control rate of both groups ( χ2 = 1.56, P = 0.212). The levels of serum CEA, SCCA and CYFRA21-1, and the positive expression rates of p40, p63, and CK5/6 in the two groups after treatment were lower than those before treatment (all P < 0.05); and the scores of physiological status, functional status, additional concern in FACT-L scores and the total score of the scale after treatment were higher than those before treatment (all P < 0.05). There were no statistically significant differences in the incidence of adverse reactions including thrombocytopenia, neutropenia, leukopenia, anemia, fever of the two groups (all P > 0.05). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.82-12.75), 5.1 months (95% CI: 3.14-12.26),respectively in the observation group and the control group, and the difference in the median PFS time was statistically significantly of both groups ( χ2 = 4.21, P = 0.040). The median overall survival (OS) time was 12.9 months (95% CI: 6.25-15.46), 9.7 months (95% CI: 4.74-13.02), respectively in the observation group and the control group, and the difference in the median OS time was statistically significantly of both groups ( χ2 = 4.43, P = 0.035). Conclusions:Deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous NSCLC with driver gene negative and PD-L1 expression positive can effectively reduce the serum tumor markers levels and positive expression rate of immunohistochemical markers, improve the quality of life of patients, and increase the short-term and long-term efficacy.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To evaluate and summary the relevant evidence of emergency target blood pressure management in acute aortic dissection, so as to provide guidance for the evidence-based practice of emergency target blood pressure management.Methods:According to the "6S" evidence pyramid model, the evidence about emergency target blood pressure management of acute aortic dissection in various databases and professional association websites at home and abroad was retrieved, including clinical decision, guidelines, expert consensus, systematic evaluation, randomized controlled trial, cohort study, case series, etc. Two researchers used corresponding literature quality evaluation tools to evaluate the quality of the included literature, extracted and summarized the evidence of the literature above grade B.Results:A total of 22 articles were included in this study, including 6 clinical decisions, 5 guidelines, 7 expert consensus, 1 systematic evaluation, 1 randomized controlled trial, 1 cohort study and 1 case series, forming 37 best evidences, including 9 topics such as target value setting, management strategies, disease observation, medical history collection, monitoring methods, vasoactive drugs, non vasoactive drugs, auxiliary examination, health education.Conclusions:The summarized best evidence provides a reference for emergency medical staff to manage the emergency target blood pressure of acute aortic dissection. It is recommended that emergency medical staff follow the summarized best evidence to formulate an individualized target blood pressure management scheme for patients.

Objective: To evaluate the effects of overweight and obesity intervention in the health-promoting school model and to provide reference for effective prevention and control of overweight and obesityin middle Schools. Methods: Using stratified cluster random sampling, 10 middle schools in Sanmenxia City were randomly divided into intervention group and control group. In the intervention group and the control group, one middle school and one high school were randomly selected. The students from the two classes randomly selected in the first and second grades in the four schools that were selected, the questionnaire survey and medical examination was conducted before and after the intervention to evaluate the intervention effect. Results: After intervention, the ratio of overweight and obesity of the intervention group decreased from 22.70% before intervention to 17.45%, statistical significance(χ 2=4.11, P<0.05), and the ratio of overweight and obesity of the control group increased from 22.39% before intervention to 22.91%, no significant difference(P>0.05). After the intervention, the response rates of limiting red meat, fried food and sugarsweetened beverages were all higher than those before the intervention, the differences were statistically significant (χ 2=125.73, 10.69, 208.55, 170.66, 50.01, P<0.01). Conclusion The comprehensive intervention measures of overweight and obesity in the model of health promotion school can encourage students to develop healthy behaviors and effectively prevent and control middle school students from overweight and obesity, and it is easy to form a long-term intervention mechanism.

Objective:To investigate the predictive value of serum soluble urokinase-type plasminogen activator receptor (suPAR) combined with alpha-fetoprotein (AFP) and model for end-stage liver disease (MELD) score in short-term prognosis assessment of patients with chronic hepatitis B (CHB) related acute-on-chronic liver failure (ACLF).Methods:From January 2018 to May 2020, 66 patients with CHB related ACLF from Fuzhou First People′s Hospital were enrolled. After 90 days of follow-up, the patients with CHB related ACLF were divided into death group and survival group according to the outcome. Meanwhile, 30 patients with CHB were enrolled by simple random sampling method. The differences of serum suPAR in patients with CHB related ACLF and patients with CHB were analyzed. The values of suPAR, AFP and MELD score were compared between death group and survival group in patients with CHB related ACLF. The predictive value of suPAR, AFP, MELD score, Child-Turcotte Pugh score (CTP score) and suPAR combined with AFP and MELD score in the short-term prognosis of patients with CHB related ACLF were analyzed by area under the receiver operator characteristic curve (AUROC). Data were analyzed by two independent sample t test or non-parametric test. Results:The serum suPAR level of patients with CHB related ACLF was (9.6±0.8) ln ng/L, which was higher than that of patients with CHB ((8.0±0.3) ln ng/L). The difference was statistically significant ( t=14.533, P<0.01). The suPAR and MELD score of patients with CHB related ACLF in the death group were (9.9±0.7) ln ng/L and 29.6 (7.1) points, respectively, which were higher than those in the survival group ((9.4±0.7) ln ng/L and 21.0 (5.0) points, respectively). The AFP level in the death group was 45.9 (108.1) μg/L, which was lower than that in the survival group (209.3 (187.1) μg/L). There were significant differences in suPAR ( t=2.895, P=0.005), MELD score ( Z=4.708, P<0.01) and AFP ( Z=3.051, P<0.01) between the death group and the survival group. AUROC of suPAR (0.741, P=0.001), AFP (0.724, P=0.002) and MELD score (0.885, P<0.01) had predictive value for death in patients with CHB related ACLF. The sensitivities of suPAR, AFP, MELD score, CTP score and suPAR combined with AFP and MELD score were 84.6%, 73.1%, 88.5%, 96.2% and 84.6%, respectively, and the specificities were 75.0%, 72.5%, 70.0%, 52.5% and 92.5%, respectively. The AUROC of suPAR combined with AFP and MELD score was 0.871 ( P<0.01), which was higher than that of CTP score (0.793, P<0.01). Conclusions:Serum suPAR is increased in patients with CHB related ACLF. SuPAR combined with AFP and MELD score could apply in the prognostic value for patients with CHB related ACLF.

Objective: To analyze the current status of epidemiological study of burns in China, and to explore the related strategies. Methods: Retrospective or cross-sectional scientific articles in Chinese or English on epidemiological study of burns in China published from January 2005 to December 2015 were systemically retrieved from 4 databases. The databases include PubMed, Embase, China Biology Medicine disc, and Chinese Journals Full-text Database. From the results retrieved, data with regard to publication year, journal distribution, number of institutions participated in the study, affiliation of the first author and its location, and admission time span and age of patients in all the scientific articles were collected. Furthermore, the definition of age range and the grouping method of age of pediatric patients in English articles on epidemiological study of pediatric burns of China were recorded. Data were processed with descriptive statistical analysis. Results: A total of 256 scientific articles conforming to the study criteria were retrieved, among which 214 (83.59%) articles were in Chinese, and 42 (16.41%) articles were in English; 242 (94.53%) articles were retrospective studies, and 14 (5.47%) articles were cross-sectional studies. During the 11 years, the number of the relevant articles was fluctuant on the whole. The scientific articles were published in 130 journals, with 42 English articles in source journals for SCIENCE CITATION INDEX EXPANDED-JOURNAL LIST, accounting for 16.41%, and 116 Chinese articles in Source Journal for Chinese Scientific and Technical Papers, accounting for 45.31%. Totally 215 (83.98%) articles were single-center studies, and 29 (11.33%) articles were multicenter studies which were conducted by three or more centers. The number of affiliations of the first author of articles was 161 in total. The top 10 institutions regarding the article publishing number published 58 articles, accounting for 22.66%. Scientific articles on epidemiological study of burns were retrieved with location of affiliation of the first author in 31 provinces, autonomous regions, and municipalities directly under the Central Government in Mainland China, and also in Taiwan Province and Hong Kong Special Administrative Region, among which Shanghai ranked first with 24 (9.38%) articles published. The admission time span of patients in the articles ranged from 3 months to 47 years, with 120 (46.87%) articles from 3 months to 5 years, 79 (30.86%) articles from 6 to 10 years, and 57 (22.27%) articles more than 10 years, respectively. Regarding the age of patients in the study, 123 articles were on epidemiological study of pediatric burns, and 16 articles on epidemiological study of elderly burns, accounting for 48.05% and 6.25%, respectively. Further analysis of articles on epidemiological study of pediatric burns in English showed that there was no standard definition of age range or unified grouping method of age for pediatric burn patients. Conclusions The epidemiological study of burns in China has been carried out nationwide, but the number of institutions conducted relevant study is not that much, and multicenter epidemiological studies remain scanty. The quality of the articles needs to be further improved. The epidemiological study of elderly burns is relatively deficient and calls for more attention. The epidemiological study of burns in China lacks regularity or continuity in time scope. There is an urgent need for the guideline on classification method for items of epidemiological study of burns in China so as to standardize the related research.

Objective To explore the effects of bundle care on preventing cannula dislocation for tracheotomy in patients with inhalation injury. Methods Totally 51 patients who received tracheotomy in the First Affiliated Hospital of PLA General Hospital between January 2010 and December 2014 were selected as a control group, while another 36 patients with inhalation injury who were admitted and received tracheotomy from January 2015 to May 2017 were selected as an observation group. Patients in the control group received conventional nursing after tracheotomy, while patients in the observation group received safely managed bundle care on the basis of conventional nursing. The incidence of unanticipated cannula dislocation after tracheotomy and before extubation were then observed between the patients in the two groups. Results The incidence of unanticipated cannula dislocation of the patients in the observation group and the control group was 2.8% (1/36) and 19.6% (10/51), respectively (χ2=5.412,P< 0.05). Conclusions Bundle care, when applied in the management of cannula for tracheotomy in patients with inhalation injury, can reduce the incidence of unanticipated cannula dislocation.

OBJECTIVETo investigate the suitable transfection condition of human epidermal cells (hECs) with human epidermal growth factor (EGF) gene by adenovirus vector (Ad-hEGF) and its effects on the biological characteristics of hECs.

METHODShECs were isolated from deprecated human fresh prepuce tissue of circumcision by enzyme digestion method and then sub-cultured. hECs of the third passage were used in the following experiments. (1) Cells were divided into non-transfection group and 5, 20, 50, 100, 150, and 200 fold transfection groups according to the random number table (the same grouping method below), with 3 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in the latter six groups were transfected with Ad-hEGF gene in multiplicities of infection (MOI) of 5, 20, 50, 100, 150, and 200 respectively. The morphology of the cells was observed with inverted phase contrast microscope, and expression of green fluorescent protein of the cells was observed with inverted fluorescence microscope at transfection hour (TH) 24, 48, and 72. (2) Another three batches of cells were collected, grouped, and treated as above, respectively. Then the transfection rate of Ad-hEGF gene was detected by flow cytometer (n=3), the mass concentration of EGF in culture supernatant of cells was detected by enzyme-linked immunosorbent assay (n=6), and the proliferation activity of cells was detected by cell counting kit 8 (CCK8) and microplate reader (n=6) at TH 24, 48, and 72, respectively. (3) Cells were collected and divided into non-transfection group and transfection group, with 6 wells in each group. Cells in non-transfection group were cultured with culture supernatant of cells without transfection, while cells in transfection group were cultured with culture supernatant of cells which were transfected with Ad-hEGF gene in the optimum MOI (50). CCK8 and microplate reader were used to measure the biological activity of EGF secreted by cells on culture day 1, 3, and 5. (4) Cells were collected and divided into non-transfection group and transfection group, with 12 wells in each group. Cells in non-transfection group were not transfected with Ad-hEGF gene, while cells in transfection group were transfected with Ad-hEGF gene in the optimum MOI (50). The expression levels of cytokeratin 14 (CK14) and CK19 of cells were measured by immunofluorescence staining at TH 24. (5) Cells were collected, grouped, and treated as in (4), with 6 wells in each group. At post scratch hour (PSH) 0 (immediately after scratch), 12, 24, and 48, the migration distance of cells was observed and measured with inverted phase contrast microscope. Data were processed with analysis of variance of factorial design, analysis of variance for repeated measurement, and LSD test.

RESULTS(1) At TH 24 and 48, morphology of cells in each transfection group and non-transfection group were similar. Compared with that in non-transfection group, the cell debris increased significantly in 200 fold transfection group at TH 72. At TH 24, 48, and 72, the expression of green fluorescent protein was not seen in cells of non-transfection group, whereas it increased in cells of transfection group over transfection time. (2) The transfection rate of Ad-hEGF gene of cells in each transfection group increased gradually over transfection time. At TH 72, the transfection rates of Ad-hEGF gene of cells in 50-200 fold transfection groups were all above 90%, while the transfection rates of Ad-hEGF gene of cells in non-transfection group, 5, and 20 fold transfection groups were (0.51±0.20)%, (62.44±6.23)%, and (75.00±5.43)% respectively, which were obviously lower than the rate in 50 fold transfection group [(93.12±2.55)%, with P values below 0.01]. The mass concentration of EGF in culture supernatant of cells in each transfection group increased gradually over transfection time. At TH 72, the mass concentration of EGF in culture supernatant of cells in 50 fold transfection group was obviously higher than that in each of the other groups (with P values below 0.01). The proliferation activity of cells in each group at TH 24 and 48 was similar (with P values above 0.05). At TH 72, the proliferation activity of cells in 200 fold transfection group was obviously lower than that in other groups (with P values below 0.05). (3) On culture day 1, the biological activity of EGF secreted by cells in two groups was similar (P>0.05). On culture day 3 and 5, the biological activity of EGF secreted by cells in transfection group were obviously higher than that in non-transfection group (with P values below 0.01). (4) At TH 24, the expression levels of CK14 and CK19 of cells in transfection group were higher than those in non-transfection group. (5) The width of scratch in two groups was nearly the same at PSH 0. At PSH 12-48, the migration distance of cells in transfection group was obviously longer than that in non-transfection group (with P values below 0.01).

CONCLUSIONSThe suitable range of MOI of hECs transfected with Ad-hEGF gene is 50-150, and 50 is the optimum. hECs transfected with Ad-hEGF gene with MOI 50 can effectively express the EGF gene and keep its good abilities of proliferation, differentiation, and migration, as well.

Adenoviridae ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; EGF Family of Proteins ; genetics ; metabolism ; Epidermis ; cytology ; Genetic Vectors ; Humans ; Keratins ; metabolism ; Male ; Transfection