1.Value of synthetic MRI in the differential diagnosis of parotid gland tumors
Zanxia ZHANG ; Shujian LI ; Yong ZHANG ; Weijian WANG ; Manli SONG ; Wenhao WANG ; Baohong WEN ; Jingliang CHENG
Journal of Practical Radiology 2024;40(3):361-364
Objective To investigate the application value of quantitative relaxation parameters based on synthetic MRI technology in the differential diagnosis of parotid gland tumors.Methods Conventional MRI and synthetic MRI data of 59 patients with patho-logically confirmed parotid gland tumors were analyzed retrospectively.T1,T2,and proton density(PD)values of the tumor were extracted from T1,T2 and PD mapping.The differences in quantitative relaxation parameters of pleomorphic adenomas,Warthin tumors,and malignant tumors were further compared.Diagnostic performance of each quantitative relaxation parameter was assessed and com-pared via receiver operating characteristic(ROC)curve and DeLong test.Results T2 value was significantly higher in pleomorphic adenomas than that in malignant tumors(P<0.05).The T1,T2,and PD values of pleomorphic adenomas and malignant tumors were significantly higher than those of Warthin tumors(P<0.05).The area under the curve(AUC)of the T2 value in differentia-ting pleomorphic adenomas from malignant tumors was 0.794.The AUC for T1 value(0.939)in differentiating Warthin tumors from malignant tumors was significantly higher than that of T2(0.873,P=0.341)and PD(0.927,P=0.891)values,without sta-tistically significant difference.The AUC for T2 value(0.968)in differentiating pleomorphic adenomas from Warthin tumors was significantly higher than that of T1(0.931,P=0.360)and PD(0.876,P=0.120)values,without statistically significant difference.Conclusion Quantitative relaxation parameters based on synthetic MRI technology may contribute to differentiating pleomorphic adenomas,Warthin tumors,and malignant tumors of the parotid gland.
2.Clinical application of enhanced recovery after surgery combined with intestinal fluid reflux in enterostomy in newborn
Wenyue LIU ; Xiaoxia WU ; Hui ZHANG ; Xue SUN ; Baohong ZHAO ; Yuanyuan JIN ; Hongxia REN
Chinese Journal of Neonatology 2024;39(3):145-149
Objective:To study the clinical value of enhanced recovery after surgery(ERAS) strategy combined with early intestinal fluid reinfusion among neonates receiving jejunostomy due to intestinal obstruction.Methods:From December 2018 to December 2022, neonates with intestinal obstruction receiving jejunostomy in the Department of Neonatal Surgery of our hospital were prospectively enrolled. They were randomly assigned into ERAS group and traditional treatment (TT) group after surgery. The ERAS group was treated with ERAS strategy plus early intestinal fluid reinfusion. The TT group was treated with conventional gastrointestinal decompression, analgesia as needed and enteric fluid reinfusion according to the amount of defecation. The postoperative parenteral nutrition (PN) duration (T pn), central venous catheter (CVC) duration (T cvc), daily weight gain, duration of postoperative hospital stay (T hos), complications and readmission rate within 30 days were compared between the two groups. Results:A total of 22 cases were included in the ERAS group and 20 cases were in the TT group. T pn [(22.6±9.4) d vs. (30.7±11.3) d], T cvc [(5.9±0.8) d vs. (9.9±2.1) d] and T hos [(26.8±9.8) d vs. (33.8±11.5) d] in the ERAS group were significantly shorter than the TT group ( P<0.05). No significant difference existed in daily weight gain between the two groups ( P>0.05). The incidence of postoperative gastrointestinal mucosal bleeding in the ERAS group was significantly lower than the TT group (13.6% vs. 45.0%)( P<0.05). No significant differences existed in the following items between the two groups: feeding intolerance, PN-associated cholestasis, CVC-related bloodstream infection, intestinal fluid reinfusion-related complications, premature closure of fistula and readmission rate within 30 days (all P>0.05). Conclusions:The application of ERAS strategy plus early intestinal fluid reinfusion in neonates with enterostomy is safe and feasible, which can reduce the postoperative durations of PN, CVC and hospital stay and accelerate the recovery.
3.OCT and IVUS evaluating stent apposition and endothelialization after FD implantation in aneurysm animal models
Ji MA ; Shuhai LONG ; Jie YANG ; Zhen LI ; Haiqiang SANG ; Yi TANG ; Yuncai RAN ; Yong ZHANG ; Baohong WEN ; Shanshan XIE ; Ke CHEN ; Enjie LIU ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neuromedicine 2024;23(3):256-262
Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.
4.Real-World Study on the Clinical Efficacy of Different Medication Regimens of Wangbi Tablet (尪痹片) in the Treatment of Knee Osteoarthritis
Kuayue ZHANG ; Chao LI ; Zhuoyun WU ; Yawei DONG ; Zelu ZHENG ; Yuzhi LIU ; Jun ZHOU ; Jiaming LIN ; Yuefeng CHEN ; Baohong MI ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2024;65(22):2316-2325
ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets (尪痹片) for knee osteoarthritis (KOA) in a real-world setting, providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted, involving 2,999 KOA patients registered in 30 hospitals nationwide from January 26th, 2019, to December 17th, 2021. Based on the use of Wangbi Tablets during the observation period, patients were divided into a monotherapy group (1,507 cases) and a combination therapy group (1,492 cases), and the combination group can be further divided into Wangbi Tablets plus Chinese medicine (CM), Wangbi Tablets plus western medicine (WM), and Wangbi Tablets plus Chinese and western medicine (CM+WM) subgroups. The baseline data of patients in the monotherapy group and the combination group were compared, including age, gender, body weight, medication time, clinical stage, K-L grade, and others. Efficacy indicators included the Visual Analog Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and EuroQol five-dimensional (EQ-5D) health index, which were evaluated before and after 4-, 8- and 12-week treatment, and the difference before and after treatment was calculated after 4, 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables, and gender, age, body mass index (BMI), course of disease, K-L grade, and clinical stage were used as independent variables, when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time, the occurrence of major symptoms (including morning stiffness, joint swelling, soreness of waist and knees, fear of wind, and fear of cold) was counted, and the disappearance of symptoms at each time point was counted after 4, 8, and 12 weeks of treatment. ResultsAt baseline, there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups (P>0.05); the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group, while the proportion in the remission stage was lower (P<0.05); the VAS score was higher in the monotherapy group, and the EQ-5D index was lower (P<0.01), with no statistically significant difference in total WOMAC score between the two groups (P>0.05). Compared to those measured before treatment and at previous timepoint, the VAS score and WOMAC total score significantly decreased in both groups, while EQ-5D value increased (P<0.05). The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group, while the differences in WOMAC total score and EQ-5D value between baseline and after 4-, 8- and 12-week treatment were higher in the combination group (P<0.05). Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement (P<0.01), and compared to Wangbi Tablets monotherapy, the combination of Wangbi tablets with WM or CM had larger associations with pain improvement (P<0.05); and Wangbi Tablets had better efficacy when the course of treatment was >28 days (P<0.01). Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone (P<0.01); and the efficacy of Wangbi Tablets with a course of treatment >28 days was better (P<0.05). The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage (P<0.01); Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone (P<0.05). Before treatment, the proportion of patients with morning stiffness, soreness of waist and knees, fear of wind and chills in the monotherapy group was higher than that in the combination group (P<0.01). The proportion of main symptoms in both groups decreased after 4, 8 and 12 weeks of treatment (P<0.05). After 4 weeks of treatment, the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group, and after 12 weeks of treatment, the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group, while the disappearance rate of joint swelling and soreness of waist and knees was lower (P<0.05). ConclusionWangbi Tablets, whether used alone or in combination with other medications, is effective throughout the course of KOA, with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect, but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM, followed by combination with CM.
5.Research Progress in Pharmacological Effects of Tripterygium Wilfordii in the Treatment of Breast Cancer and Bone Metastasis
Jing ZHANG ; Jingwei LI ; Zichao CHEN ; Baohong LI ; Yixuan ZOU ; Hui LIU ; Xiuyun ZHANG ; Zhen ZHANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(8):1272-1280
Breast cancer is one of the most prevalent malignant tumors.Bone metastasis is a common complication during the entire course of breast cancer.The vicious cycle of"tumor-bone microenvironment"was easily formed,which led to the occurrence of bone-related events such as bone pain,pathological fractures,and hypercalcemia,etc.Studies have found that active ingredients of Tripterygium wilfordii exhibit the effect of anti-breast cancer and regulation of bone microenvironment,including inhibition of tumor cell proliferation and migration,inhibition of tumor angiogenesis,induction of autophagy in tumor cells,regulation of bone formation in osteoblast cell,inhibition of bone resorption in osteoclast cell,promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts,and regulation of immune microenvironment,which may be helpful to inhibit breast cancer and bone metastasis.This article systematically reviewed the research progress on pharmacological effects of Tripterygium wilfordii in preventing breast cancer and bone metastasis,analyzed the limitations and application prospects of the current research.
6.Effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats
Baohong WANG ; Yanbing ZHANG ; Xianping ZHANG ; Yuting LI ; Zhihui WU ; Rongying HU ; Shiyue ZHAO ; Hongna JIANG ; Yuwei YAO ; Jianda DONG
Chinese Journal of Burns 2024;40(6):579-588
Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.
7.A Real-World Clinical Study of Osteoking Combined with Intra-Articular Injection of Sodium Hyaluronate in Treatment of Knee Osteoarthritis
Rui QUAN ; Jun ZHOU ; Yan JIA ; Yan YAN ; Shuai GAO ; Zhi LIANG ; Ruihan LI ; Shuwen LI ; Yanqiong ZHANG ; Xisheng WENG ; Na LIN ; Baohong MI ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):72-79
ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism, so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking, the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system", and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions, including the Third Affiliated Hospital of Beijing University of Chinese Medicine, Peking Union Medical College Hospital, Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital, from May 1, 2020 to December 31, 2021, were selected in the system. It included 60 patients treated with Osteoking and joint injection, and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score, visual analogue (VAS) pain score, individual types of pain symptoms (cold pain, hot pain, tingling, dull pain, soreness) and other TCM symptoms were observed and compared between the two groups, and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission, this study used the "Bone Injury Cross Database (
8.Clinical Study of Osteoking Combined with Non-Steroidal Anti-inflammatory Drugs in Treatment of Knee Osteoarthritis
Zhi LIANG ; Jun ZHOU ; Rui QUAN ; Shuai GAO ; Ruihan LI ; Shuwen LI ; Baohong MI ; Yanqiong ZHANG ; Na LIN ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):80-86
ObjectiveTo explore the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis based on real-world data and provide a basis for clinical medication. MethodFrom May 2020 to December 2021, the data of a total of 1 002 patients with knee osteoarthritis who did not undergo knee joint replacement surgery was collected through the registration method. 952 patients were ultimately included, including 133 cases orally taking Osteoking combined with non-steroidal anti-inflammatory drugs as the observation group and 73 cases orally taking non-steroidal anti-inflammatory drugs alone as the control group. Statistical analysis was conducted on the baseline data, VAS scores, WOMAC scores, and other items. The visit point is the 4th and 8th weeks after registration. In order to further elucidate the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis, the effective components of Osteoking and the relevant gene sets of non-steroidal anti-inflammatory drugs and knee osteoarthritis were obtained through network pharmacology methods and retrieval in bone injury cross database, TCMSP, and other databases. Venn analysis was performed on the relevant gene sets, and a PPI network diagram was constructed. Then key core targets were screened out, and enrichment GO and KEGG enrichment analyses were conducted. ResultThe VAS score of the observation group decreases by an average of (-2.79±1.206) scores in the 4th week, which is better than the control group [(-2.73±1.575) scores, P<0.05]. The VAS score of the observation group decreases by an average of (-3.97±1.308) scores in the 8th week, which is better than the control group [(-3.89±1.822) scores, P<0.05]. The total WOMAC score of the observation group decreases by an average of (-52.07±21.677) scores points in the 8th week, which is significantly better than the control group [(-46.75±25.368) scores, P<0.05]. The observation group has an average decrease of (-10.99±4.229) scores in WOMAC (pain) score in the 8th week, which is better than the control group [(-10.03±5.535) scores, P<0.05]. The observation group has an average decrease of (-1.49±2.901) in WOMAC (stiffness) score in the 4th week, which is better than the control group [(-0.92±1.998) scores, P<0.05], and the observation group has an average decrease of (-1.90±3.200) scores in WOMAC (stiffness) score in the 8th week, which is better than the control group [(-1.26±2.230) scores, P<0.05]. The observation group shows an average decrease of (-39.17±16.562) scores in WOMAC (joint function) score in the 8th week, which is significantly better than the control group [(-35.47±20.098) scores, P<0.05]. According to network pharmacology analysis, the core network target of Osteoking in treating knee osteoarthritis is manifested as regulating signal pathways such as signal transduction transcription activator 3(STAT3), vascular endothelial growth factor A(VEGFA), tumor necrosis factor (TNF) to regulate cell signaling, angiogenesis, chondrocyte proliferation and migration, and inflammatory cells, thereby inhibiting inflammatory reactions, reducing damage, and delaying the development of the disease. ConclusionAfter a 4-week and 8-week course of treatment for knee osteoarthritis with Osteoking combined with non-steroidal anti-inflammatory drugs, there is a significant therapeutic effect on relieving pain and joint stiffness and improving joint function. In network pharmacology, Osteoking is involved in regulating inflammatory factors, metabolic response-related biological processes, the proliferation and apoptosis of chondrocytes, etc. in the treatment of knee osteoarthritis, resulting in anti-inflammatory and analgesic effects and improving joint mobility and joint stiffness. Therefore, it is worthy of clinical promotion and application.
9.Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster.
Yong KE ; En ZHANG ; Jianming GUO ; Xiaoxiao ZHANG ; Lei WANG ; Duo CHEN ; Xinkui FANG ; Jianwei ZHU ; Feng LI ; Tao SUN ; Baohong ZHANG
Acta Pharmaceutica Sinica B 2023;13(12):4856-4874
COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.
10.Comparison of drug susceptibility of and drug resistance mutations in fluconazole-resistant Candida albicans strains from superficial and deep infections
Tiantian DING ; Baohong CUI ; Shuhong MI ; Yang ZHANG ; Hailin ZHENG ; Jihai SHI ; Weida LIU
Chinese Journal of Dermatology 2022;55(10):874-878
Objective:To compare the in vitro susceptibility of fluconazole-resistant Candida albicans strains from superficial and deep infections to 8 antifungal drugs, and to compare drug resistance mutations in these strains. Methods:According to the Clinical and Laboratory Standards Institute (CLSI) protocol M27-A4, 26 deep infection-derived and 33 superficial infection-derived drug-resistant Candida albicans strains were tested for in vitro susceptibility to 8 antifungal drugs (fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, fluorocytosine, terbinafine, and micafungin) alone or in combination. DNA was extracted from all drug-resistant strains, and mutations in 3 drug resistance genes, including ERG3, ERG11 and FUR1, were detected by PCR. Normally distributed measurement data with homogeneous variance were compared between two groups by using two-independent-sample t test, non-normally distributed measurement data with non-homogeneous variance were compared using Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:The minimum inhibitory concentrations (MICs) of fluconazole, itraconazole, voriconazole, posaconazole and fluorocytosine all significantly differed between the superficial infection group and deep infection group (all P < 0.05) , while there was no significant difference in the MIC of amphotericin B or micafungin between the two groups (both P > 0.05) . The MIC of terbinafine was >64 μg/ml in 96.6% of the above strains, so could not be compared between groups. As combination drug susceptibility testing revealed, the combination of terbinafine with azoles (fluconazole, voriconazole, itraconazole or posaconazole) showed synergistic inhibitory effects against 15 Candida albicans strains (7 strains from deep infections, 8 strains from superficial infections) , with fractional inhibitory concentration (FIC) indices being 0.033 to 0.187; no marked synergistic effect was observed in the combinations between fluorocytosine and azoles, between fluorocytosine and amphotericin B, or between amphotericin B and fluconazole, with the FIC indices being 0.56 to 1.125. The missense mutation V351A in the ERG3 gene was identified in all the 33 (100%) superficial infection-derived strains, as well as in 13 (50%) deep infection-derived strains, and the mutation A353T in the ERG3 gene was identified in 4 (15%) deep infection-derived strains; as for the ERG11 gene, missense mutations identified in the superficial infection-derived strains included I437V (32 strains, 97%) , Y132H (23 strains, 70%) , T123I (16 strains, 48%) , K128T (6 strains, 18%) , D116E (5 strains, 15%) , A114S (4 strains, 12%) , E266D (2 strains, 6%) , G448E (2 strains, 6%) , and G465S (2 strains, 6%) , while missense mutations identified in the deep infection-derived strains included I437V (23 strains, 88%) , E266D (13 strains, 50%) , E260G (5 strains, 19%) , and V488I (4 strains, 15%) ; the missense mutation R101C in the FUR1 gene was identified in 11 (33%) superficial infection-derived strains, but not identified in deep infection-derived strains. Conclusion:The drug susceptibility and drug resistance mutations differed to some extent between superficial infection- and deep infection-derived fluconazole-resistant Candida albicans strains.

Result Analysis
Print
Save
E-mail