1.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
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.
2.Mechanism of Xinkang Prescription for Purging the Lung and Promoting Diuresis in Treating Heart Failure by Improving Phosphorylation of Phospholamban
Yubing ZHANG ; Lingjun WANG ; Ting WANG ; Puli XU ; Luyi TANG ; Hongxue LYU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1512-1519
Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9% sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.
3.Research on patient motion monitoring with domestic innovative integrated radiotherapy CybeRay ? real-time imaging for frameless stereotactic radiosurgery
Lihong CAI ; Wenbo GUO ; Jing NIE ; Yali WU ; Minjie ZHANG ; Huina SUN ; Xinsheng XU ; Gaoqing FENG ; Rui ZHANG ; Qingfang JIANG ; Yu ZHANG ; Yubing XIA
Chinese Journal of Radiation Oncology 2024;33(12):1138-1143
Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.
4.The 508th case: recurrent edema of bilateral lower extremities with proteinuria
Qiuyu XU ; Gang CHEN ; Chenhao YANG ; Ke ZHENG ; Jie MA ; Chao LI ; Xiaohong FAN ; Wei YE ; Yubing WEN ; Limeng CHEN ; Xuemei LI
Chinese Journal of Internal Medicine 2024;63(8):816-820
A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.
5.Predictive value of systemic immune-inflammation index and prognostic nutrition index in preterm infants with early-onset sepsis
Yubing PANG ; Zifan TONG ; Wenqiang LIU ; Yan XU ; Jun WANG
Chinese Pediatric Emergency Medicine 2024;31(5):327-332
Objective:To explore the predictive ability of systemic immune-inflammation index(SII)and prognostic nutrition index(PNI)for early-onset sepsis in preterm infants.Methods:Seventy preterm infants of 28 to 32 weeks,who were born in the Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2022, and transferred to neonatal intensive care unit within 1 h conforming to EOS diagnostic criteria were selected as the EOS group,and 1∶1 matched non-infected preterm infants hospitalized during the same period were selected as control group.Relevant data were collected to compare the differences regarding clinical data,blood routine indicators,C-reactive protein(CRP),serum albumin levels(ALB),SII and PNI between two groups.The ability of SII and PNI to predict EOS was evaluated by Logistic regression analysis and receiver operating characteristic(ROC)curve.Results:Compared with control group,the EOS group had lower 1-minute and 5-minute Apgar scores,higher rates of cesarean section delivery and tracheal intubation,as well as higher rates of suppurative meningitis,bronchopulmonary dysplasia,retinopathy of prematurity and intracranial hemorrhage.The levels of blood routine parameters,ALB,SII and PNI in the EOS group were lower than those in control group,while CRP was increased.The differences were all statistically significant( P<0.05).Multivariate Logistic regression analysis showed that tracheal intubation,CRP,SII and PNI were independently influential factors of EOS( P<0.05).ROC curve analysis showed that the areas under curve of SII,PNI,CRP and SII combined with PNI were 0.808(95% CI 0.730-0.886),0.792(95% CI 0.718-0.865),0.633(95% CI 0.541-0.725)and 0.866(95% CI 0.803-0.929),the sensitivity were 74.3%,64.3%,42.9%,78.6%,and the specificity were 88.6%,82.9%,81.4%,90.0%,respectively.The cut-off values of SII,PNI and CRP were 221.36,38.65 and 0.80 mg/L,respectively. Conclusion:SII and PNI have a certain predictive value for EOS in preterm infants,and their combined diagnosis efficiency is more stronger.
6.Comparison of effects of different anticoagulants on the release of growth factor and injection pain of platelet-rich plasma in SD rats
Li CHEN ; Guangya LIU ; Yubing XU ; Zhanhong ZHU ; Yanhui LI ; Guiqiu SHAN ; Mou ZHOU
Chinese Journal of Blood Transfusion 2023;36(8):660-664
【Objective】 To investigate the effects of different anticoagulants on platelet-rich plasma(PRP) release content of growth factor and injection pain. 【Methods】 A total of 15 voluntary blood donors were selected, with each blood donor using four kinds of anticoagulant tubes with EDTA-K
7.Preparation and preliminary evaluation of sodium alginate/agarose/carboxymethyl chitosan spray film dressing carrying platelet rich plasma for wound repair
Yubing XU ; Zhanhong ZHU ; Guangya LIU ; Li CHEN ; Zijing ZHU ; Mou ZHOU ; Guiqiu SHAN
Chinese Journal of Blood Transfusion 2023;36(2):136-140
【Objective】 To develop a spray-on membrane dressing for wound repair containing platelet rich plasma (PRP) sodium alginate (SA)/agarose(AG)/carboxymethyl chitosan (CMCS). 【Methods】 SA/AG/ CMCS were mixed in different proportions to prepare biodegradable quick setting spray (BQSS) by blending film method, and the film-forming time, moisture retention and compression resistance of the prepared BQSS were tested. Then PRP and BQSS were mixed in the proportion of 3∶7, 4∶6, 5∶5, 6∶4 and 7∶3 to prepare PRP-BQSS spray film dressings. The film-forming time, moisture retention, compressive strength, porosity and slow-release effect of growth factors of PRP-BQSS spray film dressings were studied. 【Results】 In the preparation of BQSS compound spray film solution, when SA, AG, CMCS and sterile distilled water were 0.6∶0.6∶0.6∶98.2g, the film-forming time (7.73±0.31) s, moisture retention (75. 54±3.03) % and compression resistance (791.00±68.02) g of the spray-film dressing were the best. The basic properties of PRP-BQSS spray-on film dressings and the release of growth factors show that PRP-BQSS spray-on film dressings can exist in different forms, and with the decrease of PRP concentration percentage, its film-forming time, moisturizing performance and compressive strength showed an upward trend. When the PRP content is 30%, the porosity of the dressing is the highest, about(84.34±0.90)%. The release of platelet-derived growth factor-AA(PDGF-AA), platelet factor-4(PF-4) and transforming growth factor beta (TGF-β) was in a slow upward trend, and the release of the three growth factors was higher than that of PRP group in 48 hours. 【Conclusion】 The preparation method of PRP-BQSS spray film dressing designed in this study is simple and mild, and can form a film quickly, with good biological properties and better growth factor inhibition and sustained-release effect.
8.Influencing factors of clinical efficacy of autologous platelet-rich plasma in the treatment of androgenetic alopecia
Guangya LIU ; Yubing XU ; Zhanhong ZHU ; Li CHEN ; Bo ZHENG ; Mou ZHOU ; Guiqiu SHAN
Chinese Journal of Blood Transfusion 2022;35(12):1243-1247
【Objective】 To analyze the influencing factors of clinical efficacy of autologous platelet-rich plasma in the treatment of androgenetic alopecia. 【Methods】 From January, 2019 to December, 2021, 151 outpatients with androgenetic alopecia were treated in our hospital. All patients were treated with autologous PRP injection once a month and planned to received injection for 4-6 occasions. According to the hair growth before and after treatment, the treatment results were evaluated. The influencing factors in the treatment results were grouped and analyzed, including the treatment numbers (divided into 1-6 occasions), the grade of alopecia(three grades: mild, moderate and severe alopecia) and the Plt concentration in PRP[five grades(×109/L): extremely low concentration (<800), low concentration (801-1 000) and medium concentration (1 001-1 200), high concentration(1 201-1 500)and extremely high concentration(>1 501)]. 【Results】 The correlation coefficient between the number of treatments and the effective rate was pearson=0.986, P<0.001, showing a positive correlation. There was a statistical difference in the total number of treatments between groups (P<0.01). As to the severity of alopecia: The effective rates of mild and moderate alopecia patients (66.67%, 56.95%) were higher than those of severe alopecia patients (35%). The difference between groups was statistically significant (P<0.01). As to the concentration of Plt in PRP: The concentration of Plt directly affected the therapeutic effect. When the Plt count was (1 200-1 500)×109/L, the effect was optimal, reaching 68.12%, which was significantly higher than the other four groups(P<0.01). The treatment numbers, alopecia grade and Plt concentration in PRP were all related to the effectiveness of treatment (P<0.05). When the OR value of treatment numbers and Plt concentration was >1, the effective rate increased by 2.619 times and 2.033 times, respectively, as treatment numbers and Plt concentration increased. When the OR value of the grade of alopecia was 0.338 (0<0.338<1), the effective rate decreased with the increase of alopecia severity; For each grade increased, the effective rate would be compromised by 0.338. 【Conclusion】 When PRP is applied to treat AGA patients, the clinical therapeutic effect will be better in patients who received more treatments, PRP with higher Plt count, and be in the early degree of hair loss. Whether the higher the concentration of Plt in PRP, the better the therapeutic effect will be, remains to be further verified.
9.Study on the repair effect of lyophilized platelet lysate products on articular cartilage injury model of rat
Guangya LIU ; Yubing XU ; Yu ZHANG ; Zhanhong ZHU ; Mou ZHOU ; Wei ZHANG ; Guiqiu SHAN
Chinese Journal of Blood Transfusion 2022;35(4):392-395
【Objective】 To discuss the repair effect of lyophilized platelet lysate (PL) products on articular cartilage injury model of rats. 【Methods】 A total of 25 SD rats were injected with typeⅡcollagenase at the right knuckle articular cavity respectively on day 1, 3 and 5 of experiment, and the modeling conditions were observed 14 days after the last injection of collagenase. The SD rats with successful modeling were randomly divided into three groups, and were injected with lyophilized PL [Group A, 1 mL/(mouse·time)], PL [Group B, 1 mL/(mouse·time)], and normal saline[Group C, 1 mL/(mouse·time)]. The above three substances were injected with corresponding drugs on day 0, 7, 14 and 21 of experiment based on the grouping conditions, and the changes of knee joint diameters of the rats from the three groups were observed and compared. On day 14 and 28, one rat in each group was randomly killed and two knuckle articular cavities of each were taken for tissue sampling, using hematoxylin-eosin staining (HE) and immunohistochemistry. 【Results】 After 14 days of modeling by injection of type Ⅱ collagenase, the proportion of successful modeling in rats was 84% (21/25), with the knee joint diameter (mm) before and after modeling at 12.84±1.14 vs 14.11±1.17(P<0.01). On day 14, 21 and 28, groups A and B were superior to group C in the knee joint diameter and activity improvement (P<0.05), with 13.33±1.16 vs 13.37±1.08 vs 14.21±1.08, 13.10±1.09 vs 13.01±1.04 vs 14.09±1.09 and 12.38±1.08 vs 12.51±1.03 vs 14.01±1.07, respectively. Histological observation showed that group A and B were superior to group C in the production and arrangement of chondrocytes and the positive expression of type Ⅱ collagen, and there was no significant difference between group A and group B. 【Conclusion】 The lyophilized PL has similar therapeutic effect to PL in the treatment and repair of articular cartilage injury, and is worthy of clinical application.
10.Application of autologous platelet-rich plasma in the treatment of postoperative bone nonunion for long bone shaft fractures during and after operation
Yubing XU ; Guangya LIU ; Xuqiong CHEN ; Zhanhong ZHU ; Mou ZHOU ; Wei ZHANG ; Guiqiu SHAN
Chinese Journal of Blood Transfusion 2022;35(3):254-257
【Objective】 To explore the clinical effects of autologous platelet-rich plasma (PRP) in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation. 【Methods】 A total of 34 patients with postoperative bone nonunion for long bone shaft fracture, who were admitted and cured in the Orthopedics Department of our hospital from January 2019 to June 2020, were selected. They were randomly divided into the experimental group(n=17) and control group(n=17). Individuals in the control were treated with autologous iliac bone alone., while the experimental group were treated with autologous iliac bone graft plus autologous PRP during and after operation. After surgery, the autogenous PRP was accurately injected with ultrasound guidance every 7 days (5 mL/person, 4 occasions in total). The clinical healing time of the fracture, the grading of callus formation and the functional rehabilitation level of limbs on the affected side at different time were observed in both groups. 【Results】 All 34 patients were followed up. In the experimental group and the control group, the clinical healing time (month) of the fracture was (5.03±1.24) vs (6.91±1.41), P<0.05. The healing rate of the fracture for 6 months and 9 months was 94%(16/17)vs 59%(10/17)and 94%(16/17)vs 82%(14/17), respectively (P<0.05). The grading of callus formation within 3, 6 and 9 months was (2.11±0.69) vs (1.53±0.80), (3.06±0.90) vs (2.59±0.87) and (3.82±0.73) vs (3.35±0.86), respectively (P<0.05). The acceptance rate of functional rehabilitation of limbs on the affected side was 82.35%(14/17)vs 76.47%(13/17), P<0.05. 【Conclusion】 The application of autologous PRP in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation can achieve good clinical treatment.

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