1.A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years.
Bo YU ; Haiyu WANG ; Guangming LI ; Junyi SUN ; Hong LUO ; Mengzhao YANG ; Yanyang ZHANG ; Ruihan LIU ; Ming CHENG ; Shixi ZHANG ; Guotao LI ; Ling WANG ; Guowu QIAN ; Donghua ZHANG ; Silin LI ; Quancheng KAN ; Jiandong JIANG ; Zhigang REN
Acta Pharmaceutica Sinica B 2025;15(3):1333-1343
Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.
2.Effects of miR-181c-5p on biological behaviors of prostate cancer cells by regulating BIRC5
Xing XING ; Shaoping CHENG ; Ying XIONG ; Zhigang HUANG ; Hao DENG
Acta Universitatis Medicinalis Anhui 2024;59(9):1543-1550
Objective To explore the effects and action mechanism of miR-181c-5p on biological behaviors of pros-tate cancer cells.Methods The pathological relationship between BIRC5,miR-181c-5p and prostate cancer was analyzed based on prostate cancer data in TCGA database.The target binding site of miR-181c-5p and BIRC5 was analyzed by miRNA target gene prediction database,and was verified by double luciferase activity assay.The ex-pression of BIRC5 protein in miR-181 c-5p overexpression cells was detected by Western blot.The prostate cancer cells PC3 and DU145 were selected to construct cell line with miR-181c-5p overexpression(miR-181c-5p group)and its negative control(miR-NC group),and qRT-PCR verification was conducted.The cells proliferation[opti-cal density at 450 nm site(OD450 nm)]was detected by CCK-8.Distribution of cell cycles and apoptosis rate were detected by flow cytometry.Expressions of proliferation and apoptosis related proteins were detected by Western blot.The cell line with miR-181c-5p/BIRC5 overexpression was constructed(miR-181c-5p+BIRC5 group).Cells growth,distribution of cell cycles,apoptosis rate and expressions of related proteins were detected by the a-bove methods.Results The expression of BIRC5 was up-regulated in prostate cancer tissues,and it was higher in patients with high tumor invasion,lymph node metastasis and recurrence.Patients exhibiting high expression of BIRC5 demonstrated poor survival rates.The expression of miR-181c-5p was down-regulated in prostate cancer tis-sues.The level of miR-181c-5p was negatively correlated with BIRC5 level,and miR-181c-5p could inhibit BIRC5 expression.In PC3 and DU145,miR-181c-5p level in miR-181c-5p group was higher than that in miR-NC group(P<0.05);OD450 nm and percentage of S-phase cells were lower than those in miR-NC group(P<0.05),per-centage of cells in G0/G1 phase;apoptosis rate and expressions of BAX,caspase-3 and PARP proteins were higher than those in miR-NC group(P<0.05);expressions of CDK2,CCNB1 and BCL-2 proteins were lower than those in miR-NC group(P<0.05).The expression of BIRC5 protein and OD450 nm in miR-181 c-5p+BIRC5 group were higher than those in miR-181c-5p group(P<0.05),percentage of cells in G0/G1 phase was lower than that in miR-181c-5p group(P<0.05);percentage of S-phase cells was higher than that in miR-181c-5p group(P<0.05);apoptosis rate was lower than that in miR-181c-5p group(P<0.05);expressions of CDK2,CCNB1 and BCL-2 proteins were higher than those in miR-181c-5p group;expressions of BAX,caspase-3 and PARP proteins were lower than those in miR-181 c-5p group.Conclusion miR-181-5p can inhibit the proliferation of human pros-tate cancer cells by targeting BIRC5,block cells in G0/G,phase and promote cells apoptosis.
3.Design of anterolateral thigh perforator flap aided by three-dimensional printing technique for repairing irregular extremity wounds
Chengwei GE ; Guodong JIANG ; Kai WANG ; Zhigang CHE ; Junnan CHENG ; Zhicheng TENG ; Song YUAN ; Jihui JU
Chinese Journal of Plastic Surgery 2024;40(9):946-953
Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.
4.Design of anterolateral thigh perforator flap aided by three-dimensional printing technique for repairing irregular extremity wounds
Chengwei GE ; Guodong JIANG ; Kai WANG ; Zhigang CHE ; Junnan CHENG ; Zhicheng TENG ; Song YUAN ; Jihui JU
Chinese Journal of Plastic Surgery 2024;40(9):946-953
Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.
5.Clinical Validation of a Prototype Smart Non-Invasive Pregnancy Glucose Monitor
Heqing LU ; Lirui CHENG ; Qiaoling DU ; Xiaofeng ZHANG ; Zhenzhen SUN ; Zhigang ZHU
Chinese Journal of Medical Instrumentation 2024;48(5):539-543
The aim of this study is to evaluate the effectiveness of a smart non-invasive blood glucose monitor prototype during pregnancy through clinical validation.The monitor utilizes near-infrared spectroscopy combined with AI big data analysis of photoelectric volumetric pulse wave data to achieve non-invasive monitoring of blood glucose in women during pregnancy.The research team developed a monitor that employs a sensing chip,effectively overcoming the problems of weak signals and individual differences in non-invasive blood glucose monitoring.The user experience is enhanced by visualizing the test results on the accompanying cell phone APP(application)of the smart non-invasive pregnancy blood glucose monitor.Clinical validation revealed that the non-invasive monitoring data for pregnant women aged 20~30 years significantly differed from those obtained via traditional blood glucose measurement methods,whereas no significant difference(P<0.05)was observed for pregnant women aged 31~42 years.The study concluded that further calibration of the monitor and an expansion of the sample size are necessary to enhance consistency with invasive glucose monitoring results.
6.Comprehensive management of chronic pain
Zhigang CHENG ; Fei REN ; Dong HUANG ; Qulian GUO
Journal of Chinese Physician 2024;26(9):1281-1284
Chronic pain is a disease that seriously affects people′s health and quality of life. Solving the challenges faced by chronic pain management, finding effective treatment methods, and improving the quality of life of chronic pain patients are important clinical issues that urgently need to be addressed. This article summarizes the etiology diagnosis, multidimensional evaluation, personalized treatment, prevention, and translation of pain research results for chronic pain, and looks forward to future treatment strategies for chronic pain.
7.Clinical efficacy of ultrasound-guided spinal nerve block and paraverteral nerve block in treating postherpetic neuralgia
Kai ZHANG ; Jiangang LUO ; Xiaoye ZHU ; Mengqi LI ; Zhigang CHENG ; Fei REN ; Nianyue BAI ; Yunjiao WANG ; Qulian GUO
Journal of Chinese Physician 2024;26(9):1308-1312
Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.
8.Comparison of the efficacy of amide proton transfer-weighted imaging and time-dependent diffusion MRI for the diagnosis of malignant breast lesions
Xiaoyan WANG ; Yan ZHANG ; Jingliang CHENG ; Liangjie LIN ; Zhigang WU ; Ying HU ; Yong ZHANG ; Anfei WANG ; Ying LI ; Ruhua WANG ; Kun ZHANG ; Wenhua ZHANG ; Baojing WANG
Chinese Journal of Radiology 2024;58(6):611-619
Objective:To compare the efficacy of amide proton transfer-weighted (APTw) imaging with time-dependent diffusion MRI (td-dMRI) in the diagnosis of malignant breast lesions.Methods:This study was a cross-sectional study. The clinical, pathological and imaging data of patients with breast lesions admitted to the First Affiliated Hospital of Zhengzhou University from March to August 2023 were prospectively analyzed. All patients firstly underwent T 2WI, diffusion-weighted imaging, followed by dynamic contrast-enhanced MRI (DCE-MRI), and finally APTw imaging and td-dMRI were performed for breast lesions using DCE-MRI as reference. Reconstructed images from APTw imaging measured lesions with a frequency shift of 3.5 ppm asymmetric magnetic susceptibility MTR asym(+3.5 ppm). The apparent diffusion coefficient (ADC) values at different oscillating frequency gradients (ADC PGSE, ADC 17 Hz, ADC 33 Hz values) were measured using reconstructed td-dMRI images. Independent sample t-test was used to compare APTw imaging, td-dMRI parameter differences between benign and malignant breast tumors, breast malignant tumors with different molecular types [estrogen receptor (ER) negative and positive, progesterone receptor (PR) negative and positive, human epidermal growth factor receptor (HER-2) negative and positive, proliferation index (Ki-67) low and high expression] and different histological grades (grade Ⅱ and Ⅲ). Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the efficacy of APTw imaging and td-dMRI parameters in differentiating benign and malignant breast tumors, molecular classification and histological grading of malignant breast lesions. Results:There were 171 lesions in 171 patients, including 103 malignant lesions and 68 benign lesions. Histological grades were grade Ⅱ in 51 cases and grade Ⅲ in 38 cases of 89 cases of invasive carcinoma. Totally 98 cases of malignant lesions were included in molecular typing analysis, 36 cases were ER negative and 62 cases were ER positive. PR was negative in 51 cases and positive in 47 cases. There were 33 negative HER-2 patients, 65 positive HER-2 patients. There were 50 cases of low Ki-67 expression and 48 cases of high Ki-67 expression. The MTR asym(+3.5 ppm) value of malignant breast lesions was higher than that of benign lesions ( t=5.76, P<0.001), and the ADC PGSE, ADC 17 Hz and ADC 33 Hz values were lower than those of benign breast lesions ( t was 4.84, 4.62, 4.01, respectively, all P<0.001). MTR asym(+3.5 ppm) had the highest AUC value (0.83) and the highest specificity (90.38%), and ADC PGSE had the highest sensitivity (85.86%). There were no significant differences in MTR asym(+3.5 ppm), ADC PGSE, ADC 17 Hz and ADC 33 Hz between grade Ⅱ and grade Ⅲ histological grades of malignant breast lesions (all P>0.05). The ADC PGSE value of ER negative was higher than that of ER positive ( t=2.34, P=0.018), and the AUC for distinguishing ER positive from negative was 0.64. The ADC PGSE and ADC 17 Hz values of PR negative were higher than those of PR positive ( t=2.87, 2.81, P=0.004, 0.006, respectively), and their AUCs for identifying PR positive versus negative breast malignant lesions were 0.68 and 0.67, respectively. The ADC 33 Hz value of negative HER-2 was lower than that of positive HER-2 ( t=3.00, P=0.003), and the AUC for distinguishing positive and negative HER-2 was 0.67. There were no significant differences in other parameters among different subtypes of breast malignant lesions (all P>0.05). Conclusion:Compared with td-dMRI, APTw imaging is more effective in differentiating benign and malignant lesions of breast tumors, and ADC values at different gradient oscillation frequencies obtained by td-dMRI show better diagnostic efficacy in differentiating different molecular types of breast malignant lesions.
9.Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging
Fangying FAN ; Wenzhen DING ; Fangyi LIU ; Zhigang CHENG ; Zhiyu HAN ; Xiaoling YU ; Ping LIANG ; Jie YU
Chinese Journal of Hepatology 2024;32(3):208-213
Objective:To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation.Methods:A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups.Results:The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants ( P ?0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants ( P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion:LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.
10.Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study
Yanchun LUO ; Manlin LANG ; Wenjia CAI ; Zhiyu HAN ; Fangyi LIU ; Zhigang CHENG ; Xiaoling YU ; Jianping DOU ; Xin LI ; Shuilian TAN ; Xuejuan DONG ; Ping LIANG ; Jie YU
Chinese Journal of Hepatology 2024;32(4):332-339
Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?0.001, especially for liver cancer 3.1~5.0 cm ( P ?0.001). Conclusion:Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.


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