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.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
3.Research progress of nitroxide radical derivatives and their biological activities
Qili ZHANG ; Xue TIAN ; Jie WANG ; Lei ZHAO ; Pengfei XIA ; Yanli XU ; Fumei XU ; Yinqiang JIA
Journal of China Pharmaceutical University 2024;55(5):673-684
Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.
4.Efficacy of horizontal plate plus raft screws above the acetabulum in the treatment of acetabular fractures combined with dome impaction in the aged patients
Zhaojie LIU ; Jian JIA ; Haotian QI ; Yuxi SUN ; Gang LI ; Wei TIAN ; Hongchuan WANG ; Shucai BAI ; Pengfei LI
Chinese Journal of Trauma 2024;40(3):221-228
Objective:To compare the efficacy of the horizontal plate plus raft screws above the acetabulum and fixation with screws only for acetabular fractures combined with dome impaction in the aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 20 aged patients with acetabular fractures combined with dome impaction, who were admitted to Tianjin hospital between May 2013 and January 2023, including 5 males and 15 females, aged 61-84 years [(72.2±7.3)years]. According to Letournel and Judet classification, 13 patients had anterior column fracture, 5 anterior column fracture combined with posterior transverse fracture and 2 two-column fracture. All the patients underwent open reduction and internal fixation through an anterior approach. Of them, 11 patients were treated with the fixation with the horizonal plate plus raft screws above the acetabulum (plate plus raft screw group) and 9 with the screws only (screw only group). The operative time, intraoperative blood loss, and intraoperative fluoroscopy times were compared between the two groups. The quality of fracture reduction was evaluated with the Matta′s radiographic criteria at 3 days after surgery and the function of the hip joint was assessed with Merle D′Aubigné and Postel scoring system at 3 months after surgery and at the last follow-up as well as the excellent and good rate at te last follow-up. The occurrence of postoperative complications was observed.Results:All the patients were followed up for 6-18 months [(13.1±3.1)months]. There were no significant differences in the operative time, intraoperative blood loss or intraoperative fluoroscopy times between the two groups ( P>0.05). According to the Matta′s radiographic criteria at 3 days after surgery, patients with anatomical reduction and satisfactory reduction accounted 6 and 5 in the plate plus raft screw group, compared to 5 and 4 respectively in the screw only group ( P>0.05). The values of Merle D′Aubigné and Postel score at 3 months after surgery and at the last follow-up were (14.0±2.4)points and (15.8±2.2)points in the plate plus raft screw group, which were higher than those in the screw only group [(11.0±2.6)points and (13.0±3.1)points] ( P<0.01). The values of Merle D′Aubigné and Postel score at the last follow-up of both groups were further enhanced from those at 3 months after surgery ( P<0.01). At the last follow-up, 3 patients were rated excellent, 6 good, 1 fair and 1 poor in the plate plus raft screw group, with an excellent and good rate of 81.8%, while in the screw only group, 3 were rated good, 2 fair and 4 poor, with an excellent and good rate of 33.3% ( P<0.05). One patient in the plate plus raft screw group and 5 in the screw only group had displacement of the dome impaction fragment combined with traumatic arthritis after surgery ( P<0.05). Conclusion:For acetabular fractures combined with dome impaction in the aged patients, the horizontal plate plus raft screw above the acetabulum can effectively improve the function restoration of the hip joint and reduce the occurrence of the displacement of the dome impaction fragment and traumatic arthritis after surgery compared to the fixation with screws only.
5.Risk factors and treatment methods of nonunion after intramedullary nailing of subtrochanteric femoral fractures: a review
Pengfei LI ; Jian JIA ; Xinlong MA
Chinese Journal of Trauma 2024;40(7):654-659
The surgical reduction and fixation of subtrochanteric femoral fractures are challenging due to its particular anatomical and biomechanical characteristics. Intramedullary nailing is the golden standard for its treatment, but postoperative bone nonunion is a common complication, resulting in limb pain and decreased mobility, which requires a second operation and greatly affects the patients′ life quality. At present, there are many studies on the risk factors of bone nonunion after intramedullary nail fixation, but the risk factors with strong correlation remain unclear and the subsequent treatment plans are diverse, without consensus. Further identification of risk factors can help to select treatment plans. To this end, the authors reviewed the research progress in the risk factors and treatment methods of bone nonunion after intramedullary nailing of subtrochanteric femoral fractures to provide references for its clinical treatment.
6.Development of the Spleen Deficiency Evidence Scale for County Residentsand Test of Reliability and Validity
Meng ZHU ; Lingjuan JIA ; Fuzhen PAN ; Huiqing CHEN ; Jing XIAO ; Pengfei SHAO ; Yuxuan GONG ; Weifang ZHENG ; Yongsheng ZHANG ; Xiaqiu WU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1939-1945
Objective This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.
7.High Expression of KIFC1 in Glioma Correlates with Poor Prognosis
Pengfei XUE ; Juan ZHENG ; Rongrong LI ; Lili YAN ; Zhaohao WANG ; Qingbin JIA ; Lianqun ZHANG ; Xin LI
Journal of Korean Neurosurgical Society 2024;67(3):364-375
Objective:
: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression.
Methods:
: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay.
Results:
: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2.
Conclusion
: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.
8.Repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness
Pengfei LIANG ; Xisheng XU ; Pihong ZHANG ; Changlong BI ; Hua ZHANG ; Mitao HUANG ; Zhiyou HE ; Jizhang ZENG ; Yun HUANG ; Jia LI ; Xu CUI ; Situo ZHOU ; Minghua ZHANG ; Xiaoyuan HUANG
Chinese Journal of Burns 2023;39(3):221-227
Objective:To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness.Methods:A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up.Results:The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis.Conclusions:Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.
9.Efficacy observation and imaging evaluation of arthroscopic repair of degenerative medial meniscus injury in middle-aged and elderly patients
Zhenfei LU ; Lei LIU ; Pengfei JIA ; Hongxia ZHOU ; Jianhua WANG
Chongqing Medicine 2023;52(23):3620-3625,3631
Objective To observe the clinical effect of arthroscopic repair of isolated degenerative medi-al meniscus injury in patients over 45 years old and to evaluate the healing after more than two years of fol-low-up through MRI.Methods A retrospective study was conducted on the clinical effects of 51 patients with isolated degenerative medial meniscus injury who underwent arthroscopic repair from January 2016 to Decem-ber 2020.The meniscus was sutured by total internal suture or total internal suture combined with internal-to-external technique.IKDC score,Tegner score and Lysholm score were recorded before operation and at the last follow-up(at least 24 months).The type and location of meniscus injury during operation,and the microscopic classification and location of cartilage injury were recorded.At the same time,MRI was used to observe the healing of meniscus and ICRS cartilage injury grading.On MRI,0-2 degree injury was defined as meniscus healing,and 3 degree injury was defined as nonunion.The clinical repair failure was judged according to the Barrett evaluation criteria.Results The average age of the patients was(57.3±8.4)years,and the average follow-up time was(55.0±15.3)months.There were 47.1%complex fissures,31.3%horizontal fissures and 21.6%other types.The Lysholm score increased from 53.5±6.4 preoperative to 87.6±7.9 postoperative,the IKDC score increased from 33.6±4.7 preoperative to 72.8±5.3 postoperative,and the Tegner score increased from 1.0±0.1 preoperative to 4.0±0.5 postoperative.Three patients were judged as clinical repair failure,and five patients had progressed cartilage injury after surgery.At the last follow-up,the meniscus healing was observed on MRI:0 degree in two cases(3.9%),1 degree in 17 cases(33.3%),2 degree in 11 cases(21.6%),3 degree in 21 cases(41.2%).Conclusion For middle-aged and elderly patients with isolated de-generative medial meniscus injury,if conservative treatment is not effective or there are mechanical obstruc-tion factors,arthroscopic meniscus repair can achieve good clinical results and low clinical repair failure rate.
10.Treatment of transverse with posterior wall fractures of acetabulum using robot-aided percutaneous anterior column screw combined with posterior plate
Pengfei LI ; Jian JIA ; Hongliang YAN ; Zhaojie LIU ; Wei TIAN ; Hongchuan WANG ; Xinlong MA
Chinese Journal of Orthopaedics 2023;43(12):782-788
Objective:To explore the effectiveness and safety of robot-aided percutaneous anterior column screw combined with posterior plate fixtation treatment for transverse acetabular fractures with posterior wall.Methods:A retrospective analysis was conducted on the data of 13 patients with transverse acetabular fractures and posterior wall fractures treated by robot-aided percutaneous anterior column screws combined with posterior plate in Tianjin Hospital from May 2016 to May 2021. There were 9 males and 4 females, aged 49.1±8.5 years (range, 25-65 years), 9 cases of vehicle accidents, 2 cases of falling injuries, 2 cases of impact injuries, 7 cases of combined posterior hip dislocations, and 1 case of sciatic nerve injury. Apply Kocher-Langenbeck approach for reduction and fixation of the posterior wall and the posterior column and indirect reduction of the anterior column. Use robot navigation for percutaneous anterior column screw fixation, and record the time of inserting anterior column screws, incision length, and complications. The quality of fracture reduction was evaluated using Matta imaging, and the degree of ectopic ossification was evaluated using Brooker classification. The Matta modified Postel Merle D'Aobigne score was used to evaluate the function at 3, 6 months after surgery and at the last follow-up.Results:All 13 patients successfully completed the surgery. The insertion time of the anterior column screw was 19.4±4.0 min (range, 17-23 min), and the incision length was 8.0±1.4 mm (range, 6-10 mm). Postoperative imaging examination showed that all anterior column screws were located within the bone canal, with a screw length of 108.3±11.2 mm (range, 90-130 mm), and no complications such as nerve or vascular injury or incision infection occurred. All 13 patients were followed up for a period of 12-36 months, with an average of 18.6 months; All fractures healed, with a healing time of 2-6 months, average 3.4 months. According to the Matta imaging evaluation method, 11 of 13 patients had anatomical reduction of fractures, and 2 were evaluated as incomplete reduction due to a 1-2 mm gap in the anterior column. The anatomical reduction rate was 84%. At postoperative 3, 6 months and the last follow-up, the modified Postel Merle D'Aobigne scores were 13.4±1.1, 15.8±1.5, and 17.0±1.7, respectively, with statistically significant differences ( F=7.78, P=0.007). The difference between the last follow-up and postoperative 3 months was statistically significant ( P=0.002), and there was no statistically significant difference compared to postoperative 6 months ( P=0.222). At the last follow-up, 8 cases were excellent, 4 cases were good, and 1 case was fair, with an excellent and good rate of 92%. There was no occurrence of ectopic ossification, traumatic arthritis, or necrosis of the femoral head. Conclusion:Robot-aided percutaneous anterior column screw combined with posterior plate treatment for transverse acetabular fractures with posterior wall is safe and effective, and is worthy of clinical promotion.

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