1.Objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease
Zhaoxi DONG ; Yang SHI ; Jiaming SU ; Yaxuan WEN ; Zheyu XU ; Xinhui YU ; Jie MEI ; Fengyi CAI ; Xinyue ZANG ; Yan GUO ; Chengdong PENG ; Hongfang LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):398-411
Objective:
To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD).
Methods:
A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status.
Results:
No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups.
Conclusion
Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.
2.Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.
Jiawen ZHOU ; Xinyue SUN ; Xuelian CHEN ; Huimin LIU ; Xiulian MIAO ; Yan GUO ; Zhiwen FAN ; Jie LI ; Yong XU ; Zilong LI
Acta Pharmaceutica Sinica B 2024;14(1):256-272
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.
3.Improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone of Fructus Aurantii on rats with damp blockage of the middle energizer
Wenhui GONG ; Yating XIE ; Li XIN ; Shihao YAN ; Beibei ZHAO ; Yuqing ZHENG ; Jingying GUO ; Jie SHANG ; Peng ZHENG ; Jinlian ZHANG
China Pharmacy 2024;35(7):819-824
OBJECTIVE To investigate the improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group, model group, positive control group (Raceanisodamine tablet, 1 mg/kg), HMF low-dose, medium-dose and high-dose groups (0.3, 0.6, 0.9 mg/kg), with 7 rats in each group. Except for the normal group, the other groups were modeled by internal and external composite factors. After successful modeling, the rats in each group were given the corresponding drug or normal saline, once a day, for 14 days. The general behavioral states such as dietary intake, water intake and mental state of the rats were observed, and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin (HE) staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected, and the expression of aquaporins (AQP3) in the gastric tissue of rats was determined. RESULTS Compared with the normal group, the dietary intake and water intake of the model group rats were significantly decreased (P<0.01), the fecal water content rate, salivary flow rate, plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly (P<0.01). Gastric tissue injury invaded the mucosal muscle layer, resulting in mucosal muscle layer rupture; pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group, the dietary intake and water intake of rats were increased in HMF groups; fecal water content rate, salivary flow rate, plasma content of aldosterone, the expression of AQP3 in gastric tissue were decreased, most of the above differences were statistically significant (P<0.05 or P<0.01). The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer, the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.
4.Disease burden and mortality forecast of prostate cancer in Wuhan in 2010-2019
Jinyi SUN ; Yaqiong YAN ; Yan GUO ; Chuanhua YU ; Jie GONG
Journal of Public Health and Preventive Medicine 2024;35(1):39-44
Objective To analyze the data of prostate cancer in Wuhan from 2010 to 2019, understand the characteristics and trends of incidence, mortality, and YLL, and provide decision-making basis for Wuhan's cancer prevention and control strategies. Methods Data on deaths and incident cases of prostate cancer in Wuhan from 2010 to 2019 and from 2013 to 2017, respectively, were collected from the Wuhan Death Monitoring System. Indicators such as incidence rate, mortality rate, and years of life lost due to premature death (YLL) of prostate cancer in Wuhan were calculated using Excel 2016 and Python. The Bayesian Age-Period-Cohort Model (BAPC) was used to predict the mortality rate of prostate cancer in Wuhan from 2020 to 2024. The trend changes were described using the annual average percentage change (AAPC). Results From 2010 to 2019, the incidence, mortality, and YLL rates of prostate cancer in Wuhan showed an overall increasing trend (AAPC >0, P <0.05). The standardized mortality and incidence rates in the central urban area were significantly higher than those in the outer urban area, and the age group of 85 and above had the highest incidence and mortality rates. The age group of 0-54 had the largest increase in incidence and mortality rates. From 2020 to 2024, prostate cancer in Wuhan is expected to continue to increase slightly (an increase of 0.94%). Conclusion The incidence, mortality, and YLL rates of prostate cancer in Wuhan are showing an overall increasing trend, and this trend may continue. The characteristics are higher in the central urban area than in the outer urban area, and higher in the older age group than in the younger age group. Targeted measures need to be taken, and screening for high-risk populations should be strengthened.
5.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
6.Honey-processed Hedysari Radix in treatment of spleen-Qi deficiency rats based on metabonomics of the cecum contents
Yu-Jing SUN ; Qin-Jie SONG ; Yan-Jun WANG ; Tian-Tian BIAN ; Yu-Gui ZHANG ; Xian-Wei LI ; Guo-Feng LI ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(4):584-588
Objective To find potential biomarkers and analyzing metabolic pathways of the treatment by honey-processed Hedysari Radix,the cecal contents of rats with spleen-Qi deficiency were used as samples for analysis.Methods Sixty male SD rats were randomly divided into blank,model,experimental and control groups.The rats in other groups except the control group were carried out by using the three-factor compound modeling method of bitter-cold diarrhea,excessive exertion and hunger and satiety disorders.Experimental group was given 12.60 g·kg-1 honey-processed Hedysari Radix;control group was given 0.63 g·kg-1 lactobacillus bifidum triplex tabletsa;control and model groups received with equal volume of distilled water for a total of 15 days.Measure body weight,anal temperature,immune organ index of rats.Ultra-pressure liquid chromatography-quadrupole-exactive-mass spectrometry technology was used to measure the levels of endogenous metabolites in cecum contents.Orthogonal partial least squares discriminant analysis and database"Kyoto Encyclopedia of Genes and Genomes"were used to identify potential differential metabolites and possible metabolic pathways.Results After the intervention,the average body weight of the experimental,control,model and blank groups was(216.87±7.85),(210.96±9.03),(159.47±5.18)and(293.51±22.98)g;anal temperature was(36.14±0.48),(35.40±0.64),(34.50±0.78)and(36.61±0.34)℃;the thymus indexes were(1.19±0.20),(1.24±0.25),(0.47±0.15)and(1.31±0.21)mg·g-1;the spleen indexes were(1.95±0.33),(2.18±0.28),(1.61±0.27)and(2.29±0.24)mg·g-1.Compared with the model group,the above indexes of the experimental group and the control group were significantly increased(all P<0.01).A total of 14 potential biomarkers of Honey-processed Hedysari Radix in treating spleen-Qi deficiency syndrome were screened out in this study,which mainly involved amino acid metabolism such as tryptophan and glutamate,riboflavin metabolism and adenosine 5'-monophosphate-activated protein kinase metabolism.Conclusion Honey-processed Hedysari Radix can further protect the intestinal mucosal barrier and reduce the intestinal inflammatory response by improving the metabolic level of cecum contents in rats with spleen-Qi deficiency in cecum contents,thus exerting the effect of strengthening the spleen and tonifying the Qi.
7.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
8.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.
9.Clinical trial of rituximab and leflunomide in the treatment of patients with systemic lupus erythematosus
Jia-Hui GUO ; Jun-Jie ZOU ; Yang-Yang WANG ; Jin-Long ZHANG ; Dan-Dan PANG ; Xiao-Yan XU
The Chinese Journal of Clinical Pharmacology 2024;40(11):1547-1550
Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89%(68 cases/74 cases)and 79.17%(57 cases/72 cases)with significant difference(P<0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P<0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51%and 5.56%without significant difference(P>0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.
10.Bioequivalence study of voriconazole injection in Chinese healthy subjects
Xin YAN ; Shuang YANG ; Xiao-Yan YANG ; An YAO ; Chang CUI ; Guo-Ping YANG ; Jie HUANG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2108-2112
Objective To evaluate the bioequivalence and safety of two voriconazole for injection in healthy Chinese subjects,and to explore the safety of the excipient sulfobutyl-β-cyclodextrin.Methods A single-center,single-dose,randomized,open-label,two-preparation,two-period,double-crossover trial design.A total of 18 healthy subjects were enrolled and administrated with a single intravenous infusion of voriconazole test drug and reference drug at 4 mg·kg-1 under fasting conditions,with a sequence determined by randomization.The concentrations of voriconazole in plasma and sulfobutyl-β-cyclodextrin in urine were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters of voriconazole in plasma,and SAS(version 9.4)software was used to calculate pharmacokinetic parameters of sulfobutyl-β-cyclodextrin in urine and bioequivalence analysis.Results Major pharmacokinetic parameters of voriconazole in plasma after a single intravenous infusion of voriconazole test drug and reference drug in 18 healthy subjects in a fasted state were as follows:Cmax were(2 177.00±399.10)and(2 265.00±378.70)ng·mL-1;AUC0-t were(14 612.07±8 182.95)and(15 144.69±7 814.02)ng·h·mL-1;AUC0-∞ were(16 217.48±10 862.78)and(16 863.18±10695.75)ng·h·mL-1;tmax were 2.00 and 1.98 h,respectively.The 90%confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the two drugs were within the equivalence range of 80.00%to 125.00%.Conclusion The two voriconazole for injection preparations were bioequivalent and safe when administered by intravenous infusion under fasting conditions in healthy Chinese subjects.


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