1.Role and Mechanism of Polyunsaturated Fatty Acids on Potassium Ion Channels
Yu-Jiao SUN ; Chao CHANG ; Zhen-Hua WU ; Yi-Fei ZHANG ; Yu-Tao TIAN
Progress in Biochemistry and Biophysics 2024;51(1):5-19
Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the KV7 family and large-conductance Ca2+- and voltage-activated K+ (BKCa) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional KV7 channels and BKCa channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on KV7 channels and BKCa channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on KV7 and BKCa channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In KV7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in KV7 channels, while in BKCa channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of KV7 and BKCa channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate KV7 and BKCa channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.
2.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
3.Robot-assisted screw fixation for unstable pelvic ring fractures
Zhen ZHANG ; Xueguang WANG ; Shengjun DUAN ; Yanbin SUN ; Bo TANG ; Daofu JIA ; Chang LI ; Houling ZHAO ; Shang LI ; Hongfei LI ; Huashui LIU
Chinese Journal of Orthopaedics 2024;44(7):470-476
Objective:To investigate the clinical efficacy of robot-assisted screw fixation for unstable pelvic ring multifocal fractures.Methods:A retrospective analysis was performed on 76 patients with unstable pelvic fractures treated with orthopaedic robot-assisted screw fixation in the Trauma Center of the Affiliated Central Hospital of Shandong First Medical University from January 2015 to June 2022, including 43 males and 33 females, aged 52.53±13.68 years (range, 16-87 years). There were 43 cases of falling injuries from high places, 22 cases of traffic accidents, 11 cases of crushing injuries and heavy objects. Fifty-five patients were employed before the injury, while 21 were not. Fractures were classified according to the Tile classification, with 72 cases classified as type B and 4 cases as type C. Robot-assisted fixation techniques included internal fixator (INFIX), anterior ring screws, sacroiliac screws, and LC-II screws. Intraoperative blood loss, fluoroscopy frequency, surgical time, and the success rate of initial guidewire placement were recorded. Fracture reduction quality was evaluated using the Matta criteria, and postoperative pelvic function recovery was assessed using the Majeed criteria.Results:A total of 150 surgical procedures were performed on 76 patients, including 34 cases of INFIX fixation, 48 cases of anterior ring screws, 61 cases of sacroiliac joint screws, and 7 cases of LC-II screws. The mean intraoperative fluoroscopy frequency was 46.63±17.50 times (range, 15-93 times). Intraoperative fluoroscopy frequency varied among different fixation techniques, with INFIX group at 16.44±4.32 times, LC-II group at 21.59±5.80 times, anterior ring screws group at 29.44±11.65 times, and sacroiliac screws group at 23.10±11.87 times. The intraoperative blood loss was 20 (10, 47.5) ml (range, 5-300 ml), and the surgical time was 105 (86, 150) min (range, 30-290 min). The mean surgical time varied among different fixation techniques. All patients were followed up for an average of 6.46±2.26 months (range, 3-16 months). Clinical healing was achieved in all patients within 6 months, with an average time of 3.14±0.50 months. At the last follow-up, fracture reduction quality assessed by the Matta score was excellent in 21 cases and good in 43 cases, with an excellent/good rate of 84% (64/76). The Majeed score was 81.82±9.14 points (range, 50-92 points). For patients who were employed before the injury, the Majeed score was 86.55±4.85 points (range, 60-92 points), with 49 cases rated as excellent, 5 cases as good, and 1 case as fair. For patients who were not employed before the injury, the Majeed score was 69.43±5.34 points (range, 50-73 points), with 18 cases rated as excellent, 2 cases as good, and 1 case as fair. The overall excellent and good rate was 97% (74/76). Among patients who underwent INFIX internal fixation, 8 cases experienced lateral femoral cutaneous nerve injury postoperatively, all of which recovered sensation after 3 months; 1 case using LC-II screws experienced screw loosening postoperatively and was advised to reduce activity, then the screw was removed after fracture healing at 6 months postoperatively; 1 case using anterior ring channel screws experienced surgical site infection postoperatively, which was controlled after debridement.Conclusion:In the treatment of unstable pelvic ring multiple fractures, robot-assisted screw fixation has less blood loss, less fluoroscopy times, high success rate of planning guide needle, satisfactory reduction quality and postoperative function.
4.Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases.
Chao WU ; Bin LIU ; Jing Cheng XIE ; Zhen Yu WANG ; Chang Cheng MA ; Jun YANG ; Jian Jun SUN ; Xiao Dong CHEN ; Tao YU ; Guo Zhong LIN ; Yu SI ; Yun Feng HAN ; Su Hua CHEN ; Xiao Liang YIN ; Qian Quan MA ; Mu Tian ZHENG ; Lin ZENG
Journal of Peking University(Health Sciences) 2023;55(1):133-138
OBJECTIVE:
To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs).
METHODS:
A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery.
RESULTS:
In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred.
CONCLUSION
For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.
Humans
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Tarlov Cysts/epidemiology*
;
Retrospective Studies
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Neoplasm Recurrence, Local/complications*
;
Cysts/surgery*
;
Pain
5.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
6.SERPINE1 as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma
Xiaopeng GUO ; Zhen SUN ; Huarong CHEN ; Junjun LING ; Houyu ZHAO ; Aoshuang CHANG ; Xianlu ZHUO
Clinical and Experimental Otorhinolaryngology 2023;16(1):75-86
Objectives:
. Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification.
Methods:
. This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.
Results:
. SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel.
Conclusion
. This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.
7.Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019.
Hui Hui GAO ; Sun Yi WANG ; Yu Chen ZHANG ; Ming Ming ZHOU ; Chun Zhen HUA ; Chang Zheng YUAN ; Li Ying SUN
Chinese Journal of Pediatrics 2023;61(11):1024-1030
Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.
Female
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Adolescent
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Child
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Humans
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Anti-Bacterial Agents/therapeutic use*
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Vancomycin/therapeutic use*
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Methicillin-Resistant Staphylococcus aureus
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Clindamycin/therapeutic use*
;
Ceftriaxone/therapeutic use*
;
Tigecycline/therapeutic use*
;
Linezolid/therapeutic use*
;
Levofloxacin/therapeutic use*
;
Retrospective Studies
;
Microbial Sensitivity Tests
;
Staphylococcus aureus
;
Staphylococcal Infections/drug therapy*
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Erythromycin/therapeutic use*
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Methicillin
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Penicillin G/therapeutic use*
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Escherichia coli
;
Drug Resistance, Bacterial
8. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
9.Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis.
Shan SHI ; Xue-Dong YANG ; Ping LUO ; Ji-Liang FANG ; Li SUN ; Li-Min XIE ; Tong YU ; Zhen-Chang WANG
China Journal of Orthopaedics and Traumatology 2023;36(12):1185-1190
OBJECTIVE:
To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH).
METHODS:
Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score.
RESULTS:
Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(β=-6.198, P=0.001) and femoral head collapse depth(β=-4.085, P=0.014) had a significant negative impact on Harris hip score.
CONCLUSION
Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.
Male
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Female
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Humans
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Adolescent
;
Young Adult
;
Adult
;
Middle Aged
;
Femur Head Necrosis/diagnostic imaging*
;
Retrospective Studies
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Femur Head/diagnostic imaging*
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Bone Transplantation/methods*
;
Magnetic Resonance Imaging
;
Treatment Outcome
10.Taste masking pharmaceutical excipients and their applications
Xiang-an-ni KONG ; Lei ZHAO ; Wen-zhen ZHAN ; Yu-xuan LI ; Chang LI ; Jia-sheng TU ; Chun-meng SUN
Acta Pharmaceutica Sinica 2023;58(11):3179-3184
The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

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