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 effect and safety of tirofiban bridging combined with aspirin for anti-platelet therapy in patients with acute cerebral infarction (ACI) beyond the thrombolytic time window.Methods:Sixty patients with ACI treated in Beijing Royal Hospital from January 2021 to September 2022 were retrospectively analyzed. Among them, 30 cases were treated with tirofiban bridging aspirin as the observation group, while 30 cases were treated with aspirin alone as the control group. The total effective rate of clinical treatment, the degree of neurological deficit, the degree of disease outcome and the incidence of adverse reactions were compared between the two groups. The degree of neurological deficit was evaluated using the National Institutes of Health stroke scale (NIHSS), and the degree of disease outcome was evaluated using the modified Rankin scale (mRS).Results:The overall effective rate in the observation group was significantly higher than that in the control group: 93.3% (28/30) vs. 66.7% (20/30), with a statistically significant difference ( χ2 = 10.97, P<0.01). Before treatment, there was no statistically significant difference in NIHSS score between the two groups ( P>0.05). However, after treatment, the NIHSS score in the observation group was significantly lower than that in the control group: (2.83 ± 1.87) scores vs. (4.93 ± 3.05) scores, indicating a significant difference ( t = -3.21, P = 0.002). No significant difference was observed in mRS score between the two groups before treatment( P>0.05). After treatment, the observation group showed significantly lower mRS score compared to the control group: 2.00 (1.00, 2.00) scores vs. 3.00 (2.00, 4.00) scores ( P = 0.006). There was no statistical difference in the incidence of adverse reactions between the observation group and control groups ( P>0.05). Conclusions:Tirofiban bridging aspirin has stronger inhibitory effect on platelet activity than simple application of aspirin for ACI patients with ultra-thrombolytic window, which can rapidly improve the degree of neurological impairment and daily living ability of patients, and the incidence of adverse reactions has not increased significantly.

Objective:To analyze the effect and safety of tirofiban bridging combined with aspirin for anti-platelet therapy in patients with acute cerebral infarction (ACI) beyond the thrombolytic time window.Methods:Sixty patients with ACI treated in Beijing Royal Hospital from January 2021 to September 2022 were retrospectively analyzed. Among them, 30 cases were treated with tirofiban bridging aspirin as the observation group, while 30 cases were treated with aspirin alone as the control group. The total effective rate of clinical treatment, the degree of neurological deficit, the degree of disease outcome and the incidence of adverse reactions were compared between the two groups. The degree of neurological deficit was evaluated using the National Institutes of Health stroke scale (NIHSS), and the degree of disease outcome was evaluated using the modified Rankin scale (mRS).Results:The overall effective rate in the observation group was significantly higher than that in the control group: 93.3% (28/30) vs. 66.7% (20/30), with a statistically significant difference ( χ2 = 10.97, P<0.01). Before treatment, there was no statistically significant difference in NIHSS score between the two groups ( P>0.05). However, after treatment, the NIHSS score in the observation group was significantly lower than that in the control group: (2.83 ± 1.87) scores vs. (4.93 ± 3.05) scores, indicating a significant difference ( t = -3.21, P = 0.002). No significant difference was observed in mRS score between the two groups before treatment( P>0.05). After treatment, the observation group showed significantly lower mRS score compared to the control group: 2.00 (1.00, 2.00) scores vs. 3.00 (2.00, 4.00) scores ( P = 0.006). There was no statistical difference in the incidence of adverse reactions between the observation group and control groups ( P>0.05). Conclusions:Tirofiban bridging aspirin has stronger inhibitory effect on platelet activity than simple application of aspirin for ACI patients with ultra-thrombolytic window, which can rapidly improve the degree of neurological impairment and daily living ability of patients, and the incidence of adverse reactions has not increased significantly.

OBJECTIVE：To st udy the improvement effects and its mechan ism of alisol B 23-acetate on glycolipid metabolism disorder in obesity model mice. METHODS ：The mice was given high-fat diet for 10 weeks to induce obesity model. Model mice were randomly divided into model group ，orlistat group （positive control ，15.6 mg/kg）， alisol B 23-acetate low-dose ， medium-dose and high-dose groups （7.5，15，30 mg/kg），with 10 mice in each group. Another 10 mice fed with normal diet were set as normal group. The mice in normal group and model group were given water intragastrically ，and administration groups were given the corresponding drugs intragastrically ，with the volume of 20 mL/kg，once a day ，for consecutive 4 weeks. After last medication，body weight ，waist circumference ，body fat ，muscle and body fluid mass were measured ；the serum levels of blood lipids indicators （TC，TG，HDL-C，LDL-C）and blood glucose were determined. The levels of PPAR-γ，NF-κB and IL-6 in liver tissue as well as serum level of TNF-α were determined by ELISA. The pathomorphological changes of visceral fat and liver tissue in mice were observed by HE staining. RESULTS ：Compared with normal group ，body weight ，waist circumference ，body fat and body fluid mass were significantly increased in model group （P＜0.01）；serum levels of TC ，TG，HDL-C，blood glucose and TNF-α，the levels of PPAR-γ，NF-κB and IL-6 in liver tissue were increased significantly （P＜0.05 or P＜0.01）；the structure of adipocytes was ruptured ，the volume of adipocytes was increased ，accompanied by inflammatory cell infiltration ；a large number of liver cells were edema ，and cytoplasm was loose and light stained，accompanied by fatty degeneration. Compared with model group ，the body weight ，body fat and body fluid mass as well as serum le vels of TG and TNF-α in alisol B 23-acetate groups were significantly reduced （P＜0.01）；the levels of TC and blood glucose in serum ，IL-6 in liver tissue were significantly decreased in alisol B 23-acetate medium-dose and high-dose groups （P＜0.05 or P＜0.01），and the level of PPAR-γ in liver tissue was increased significantly（P＜0.05 or P＜0.01）； the waist circumference and NF-κB levels in liver tissue in alisol B 23-acetate high-dose group were decreased significantly （P＜ 0.01）；serum level of HDL-C in alisol B 23-acetate medium-dose group were decreased significantly （P＜0.01）；the adipocytes were closely arranged and small in size ；the hepatocytes were mild to moderate swelling ，a small amount of cytoplasm was loose ， light stained or vacuolated ，and a small number of hepatocytes were accompanied by steatosis and small focal infiltration of inflammatory cells. CONCLUSIONS ：Alisol B 23-acetate can improve the disorder of glucose and lipid metabolism in obesity model mice ，and its mechanism may be related to the regulation of PPAR-γ，NF-κB，IL-6 levels in liver tissue and TNF-α levels in serum.

Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

OBJECTIVE: To explore the prognostic factors of patients with unresectable liver metastasis colorectal cancer after failed conversion chemotherapy. METHODS: A retrospective, case-controlled study was performed. Study subjects were 105 patients who were diagnosed with synchronous liver metastasis colorectal cancer after failed chemotherapy (metastasis evaluated as unresectable after the conversion chemotherapy) at Xinhua Hospital, Shanghai Jiaotong University from January 2012 to December 2015. Overall survival(OS) was retrospectively analyzed using Kaplan-Meier method. Log-rank test was used to compare survival among groups. Univariate and multivariate analysis was conducted for prognosis using Cox regression model. RESULTS: Of 105 cases,70 were male and 35 were female with median age of 60 years old. Twenty-one patients had right colon cancer, 41 had left colon cancer, 42 had rectal cancer and 1 had synchronous cancers(sigmoid colon and rectum). One hundred and two (97.1%) patients were cT3-4 and 90 patients were cN+ (imaging diagnosis). Eighty-nine (84.8%) patients were loaded with 2 or more liver metastases with the median maximum diameter of 48.3 mm. The patients were followed up for 3 to 43 months from the day of diagnosis. The median OS was 11 months (interquartile range, 8-18). The median OS of patients with cN0, cN1 and cN2 stage was 17, 13 and 10 months, respectively(P=0.026). The median OS of patients with single lesion, 2-3 lesions, 4-10 lesions and more than 10 lesions was 15, 15, 17 and 9 months, respectively (P=0.002). OS of patients with maximum diameter of liver metastatic lesion ≤ 50 mm, 51-100 mm and >100 mm was 15, 10 and 8 months, respectively(P=0.003). The median OS of patients with chemotherapy response of partial response (PR), stable disease (SD) and progressive disease (PD) was 17, 14 and 8 months, respectively(P<0.001). OS was 17 months in patients receiving second line chemotherapy and was 10 months in those without second line chemotherapy (P<0.001). OS in patients undergoing primary tumor resection was 13 month and in those without primary tumor resection was 9 months; the difference was not significant (P=0.060). Multivariate analysis showed that cN2(HR=2.115, 95%CI:1.089-4.109, P=0.027), the maximum diameter of liver metastatic lesion more than 100 mm (HR=3.112, 95%CI:1.455-6.657, P=0.003), chemotherapy response of PD (HR=4.435, 95%CI:2.506-7.533,P<0.001) and without second line chemotherapy(HR=4.432,95%CI:2.186-8.986, P=0.010) were independent prognostic factors. CONCLUSIONS For patients with unresectable liver metastasis from colorectal cancer after failed conversion chemotherapy, prognostic factors include cN2, the maximum diameter of liver metastatic lesion, chemotherapy response and second line chemotherapy. Whether the resection of primary tumor can prolong OS further study.
Antineoplastic Agents ; therapeutic use ; China ; Colorectal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Failure

Objective To investigate the result of colonoscopic positioning in laparoscopic treatment of colon tumors . Methods A retrospective analysis was made in 16 cases of colon tumors treated with laparoscopic colon resection from January 2014 to November 2015.During the operation, the lesion could not be locatized and the resection range could not be determinated because the serous layer was not involved or the lesion was located in the lateral abdominal wall .Transanal colonoscopic positioning of the lesion with light transmission method was carried out . Results The pathological changes were found under colonoscopy in all the 16 cases and the laparoscopic resection was successfully completed without conversion to open operation .No missed resection or incorrect resection occurred.The operation time was (112.5 ±31.0) min and the blood loss was (22.8 ±11.2) ml.Among 9 cases of preoperative pathological diagnosis of benign tumors , there were 6 cases of malignant tumors after surgery , including 4 cases of moderately differentiated adenocarcinoma , 1 case of moderate to severe atypical hyperplasia with cancerous lesions , and 1 case of moderately differentiated adenocarcinoma with mucous adenocarcinoma .A total of 15 patients were discharged from hospital at 12-24 days after the operation , whereas 1 patient was dismissed 1 month after the operation due to anastomotic fistula .The 16 patients were followed up for 3 months with no recurrence under colonoscopic examiantion . Conclusions During laparoscopic colon resection , if the tumor can not be locolized , colonoscopic positioning can help prevent missed resection or incorrect resection , which increases the indication and safety of laparoscopic and colonoscopic minimally invasive treatment .It has good clinical application value and deserves further promotion .

Objective To observe and identify the impact of a type of macro?pore bone block bioactive glass on osteo?blast in vitro. Methods Extract fluid of new bioactive glass was prepared withα?MEM culture medium as the bioactive medium group. And the concentrations of different ions were detected with Inductively Coupled Plasma?Atomic Emission Spectrometry in bioactive medium group andα?MEM medium group. MC3T3?E1 cells cultured in bioactive medium group were considered as ex?perimental group and cells cultured inα?MEM medium as control group. Giemsa and immunofluorescence staining was performed to detect the cell numbers, the karyoplasmic ratio and the average fluorescence intensity per cell. Cell proliferation and viability in different groups were detected by cell cycle analysis, MTT assay and BrdU assay, respectively. Total RNAs of cells in different groups were extracted and the expressions of ALP, OCN and collagenⅠwere measured by quantitative real time PCR. ALP stain?ing and alizarin red staining were performed to assess the differentiation and mineralization of MC3TC?E1 cells in different groups. Results The concentrations of Si and F were 40.02 ± 0.67 mg/L and 0.02 ± 0.001 mg/L in bioactive medium group, higher than 2.02±0.01 mg/L and 0.00 mg/L inα?MEM solution, and the concentration of Ca was lower than that inα?MEM solution. The con?centration of P and Na had no difference. In Giemsa staining, the cell number in 400 times field under a microscope was 106.0 ± 6.025 in bioactive medium group and 40.20 ± 3.639 inα?MEM medium group. In the immunofluorescence of vinculin, the karyo?plasmic ratio and the expression of vinculin were higher in bioactive medium group (40.85±5.720, 0.050 88±0.021 78) than inα? MEM medium group (21.93 ± 4.137, 0.023 60 ± 0.003 18). In cell cycle analysis, the proportion of cells retained in S and G2/M phase in the bioactive medium group was more than that in theα?MEM medium group after 72 hours of cell culture. In the BrdU and MTT assay, MC3T3?E1 cells in bioactive medium group both showed a higher proliferation rate with statistical significance. In MC3T3?E1 cells cultured with the bioactive medium, the expressions of osteogenesis?related genes were higher than those cultured with ordinaryα?MEM solution;in the ALP staining and alizarin red staining, the expression of ALP and the mineralization rate were higher in bioactive medium group (1.328%±0.015 36%, 2.953%±0.536 3%) than inα?MEM medium group (0.979%±0.030 59%, 1.000%±0.208 1%). Conclusion The bioactive medium promotes cell proliferation and osteoblastic differentiation of MC3T3?E1 cells, and has much more Si ions, which indicates that macro?pore bone block bioactive glass can promote cell proliferation and dif?ferentiation and has promising bioactivity.

Objective To observe the effects of the drug pair of Rhizoma Polygoni Cuspidati ( Huzhang) and Ramulus Cinnamomi ( Guizhi) on the Toll-like receptor 4 mediated myeloid differentiation factor 88 ( TLRs/MyD88) signaling pathway of rats with acute gouty arthritis induced by monosodium sodium urate (MSU) , so as to explore its therapeutic mechanism. Methods Forty-eight male SD rats were divided into normal group, modele group, blank plasmid group, positive plasmid group, Huzhang- Guizhi herb-pair (7 g/kg) group, and Huzhang-Guizhi herb-pair ( 7 g/kg) siRNA group, 8 rats in each group. The normal group, plasmid groups and model group were given physiological saline, and the left groups were given the corresponding drug by intragastric administration for 10 continuous days ( once daily ) . On the seventh day of intragastric gavage, acute gouty arthritis were induced by injection of MSU into the rat ankle joint, and normal group was injected with the samevolume of normal saline. Positive plasmid group and Huzhang-Guizhi herb-pair siRNA group were injected with the constructed siRNA-TLR4 plasmid targeting TLR4 gene ( TLR4-siRNA) to inhibit the in-vivo TLR4 gene expression. Pathological changes of the synovial tissues were detected, the contents of peripheral blood tumor necrosis factor alpha ( TNF-α) and interleukin 1 beta ( IL-1β) were detected by double antibody sandwich method, and the mRNA and protein expression levels of TLR4, MyD88, TNF receptor-associated factor 6 ( TRAF-6) in peripheral blood mononuclear cells of rats were detected by real-time fluorescence quantitative polymerase chain reaction ( PCR) and Western blot methods. The nuclear factor kappa B ( NF-κB) p65 immunoactivity was assayed by immunohistochemistry. Results Compared with the normal group, the model group had obvious hyperplasia of synovial cells and the inflammatory cell infiltration ( dominated by lymphcytes and monocytes) , and had amount of cellulose adhesive on the synovial membrane surface. Compared to the model group, positive plasmid group, Huzhang- Guizhi herb-pair group and Huzhang-Guizhi herb-pair siRNA group could obviously relieve the inflammatory cell infiltration, and improve synovial cell proliferation reaction. Compared to the normal group, serum levels of TNF-α and IL-1β, and the expression levels of TLR4, MyD88, TRAF-6 mRNA and protein in the peripheral blood mononuclear cells as well as the synovial NF-κB p65 ex pression in the model group were significantly increased ( P<0.01). Compared to the model group, positive plasmid group, Huzhang-Guizhi herb-pair group and Huzhang- Guizhi herb-pair siRNA group showed significant decrease in the levels of TNF-α, IL-1β, TLR4 MyD88, TRAF-6 and NF-κB p65 ( P<0.05 or P<0.01) . Conclusion Huzhang-Guizhi herb-pair can regulate the cytokines of the synovial membrane tissue in acute gouty arthritis rats, which may be related with its effect on inhibiting abnormal activation of TLR4-MyD88-NF-κB pathway in synovial tissue.