1.Effects of Tripterygium wilfordii multiglycoside on renal injury in rats with diabetic nephropathy
Chong ZHANG ; Chundong SONG ; Mo WANG ; Shuang LIANG ; Xiaoxiao GUO ; Hanhan ZHANG ; Peijia LI ; Ke SONG ; Chenchen CHEN
China Pharmacy 2025;36(7):815-819
OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside (TWM) on renal injury in diabetic nephropathy (DN) rats through tumor protein p53/microRNA-214 (miR-214)/UNC-51-like kinase 1 (ULK1) axis. METHODS Male SD rats were randomly divided into normal group (n=6) and modeling group (n=28); the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group, valsartan group [8.33 mg/(kg·d)] and TWM group[6.25 mg/(kg·d)], with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline, once a day, for 6 consecutive weeks. After the last medication, liver and renal function indexes [24 h urinary total protein (24 h-UTP), blood urea nitrogen (BUN), serum creatinine (SCr), albumin (ALB), alanine transaminase (ALT)], blood lipid indexes (triglycerides, total cholesterol) and blood glucose index (fasting blood glucose) in urine/blood sample of rats were detected in each group. Renal pathologic change was observed, protein and mRNA expressions of p53, ULK1, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3), and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group, the renal tubular epithelium of rats in the model group showed obvious edema, cell swelling, accompanied by lymphocyte infiltration; the levels of 24h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1, Beclin-1 protein and mRNA were significantly decreased or down-regulated (P<0.01). Compared with the model group, the histopathological damage of the kidney in rats was improved in administration groups; the levels of 24 h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 were all significantly decreased or down-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated (P<0.01). CONCLUSIONS TG can alleviate renal damage in DN rats, and improve their liver and renal function, as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.
2.The application strategies of non-uniform sampling in the structure elucidation of small molecule compounds—an instantiation using fuziline
Li-li ZHANG ; Ke ZHANG ; Jie LIU ; Chun-wang MENG ; Rui FENG ; Liang XIONG
Acta Pharmaceutica Sinica 2025;60(1):218-224
Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of
3.Analysis of The Characteristics of Brain Functional Activity in Gross Motor Tasks in Children With Autism Based on Functional Near-infrared Spectroscopy Technology
Wen-Hao ZONG ; Qi LIANG ; Shi-Yu YANG ; Feng-Jiao WANG ; Meng-Zhao WEI ; Hong LEI ; Gui-Jun DONG ; Ke-Feng LI
Progress in Biochemistry and Biophysics 2025;52(8):2146-2162
ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.
4.Construction and application of the criteria for drug utilization evaluation of low-dose rivaroxaban in atherosclerotic cardiovascular disease
Liang WU ; Wei WANG ; Yanghui XU ; Bo ZHU ; Yijun KE
China Pharmacy 2025;36(17):2176-2181
OBJECTIVE To construct and apply drug utilization evaluation (DUE) criteria for low-dose rivaroxaban in atherosclerotic cardiovascular disease (ASCVD) based on the dual pathway inhibition (DPI) antithrombotic therapy scheme, to promote clinical rational drug use. METHODS Based on the instructions and relevant guidelines of low-dose rivaroxaban (2.5 mg, bid), the Delphi method was used to establish the DUE criteria for low-dose rivaroxaban used in ASCVD. Weighted technique for order preference by similarity to an ideal solution method was used to determine the relative weights of each evaluation index, and the rationality of the filing medical records of discharged patients using low-dose rivaroxaban for ASCVD at Anqing Municipal Hospital from February 2024 to January 2025 was evaluated. RESULTS The established DUE criteria included 3 primary indicators (medication indications, medication process, medication results) and 11 secondary indicators (such as indications, contraindications, etc.). The higher weighted secondary indicators being contraindications (0.117 9) and indications (0.112 1). A total of 265 medical records were included for evaluation. The evaluation results showed that 192 cases (72.45%) had reasonable medical records, 69 cases (26.04%) had basic reasonable medical records, and 4 cases (1.51%) had unreasonable medical records; unreasonable types mainly included inappropriate combination therapy, inappropriate usage and dosage, inappropriate post- medication monitoring, and inappropriate drug switching, etc. CONCLUSIONS This study establishes a DUE criteria for low-dose rivaroxaban in ASCVD based on the DPI antithrombotic treatment regimen, and the evaluation results are intuitive, reliable, and quantifiable. The use of low-dose rivaroxaban in ASCVD patients in our hospital is relatively reasonable, but further management needs to be strengthened.
5.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
6.Celastrol ameliorates atopic dermatitis by modulating Ezrin activation
Hong-Yu JIN ; Dan-Dan WANG ; Xin-Yi SONG ; Ke-Xin XU ; Guang-Hai YAN ; Liang-Chang LI
Chinese Pharmacological Bulletin 2024;40(10):1921-1930
Aim To investigate the effect of Celastrol on the expression of Ezrin in tissues and HaCaT cells of DNCB sensitisation-induced atopic dermatitis(AD)mice.Methods BALB/c mice were taken and ran-domly divided into the control,DNCB group,Celastrol 25 μg,50 μg,75 μg treatment group,and Dex group,with 8 mice in each group;HaCaT cells were induced with TNF-α and treated with 1 μmol·L-1 Celastrol and Ezrin siRNA.The thickness of the skin on the ear and back of mice was measured by a thickness gauge,and the spleen and lymph nodes of mice were taken to observe the changes.HE and toluidine blue staining were used to observe the inflammatory cells and mast cell infiltration in mice.Flow cytometry was used to detect the levels of IL-4 and TNF-α in the lymph nodes of mice,and enzyme-linked immunosorbent was used to determine the levels of IL-4,TNF-α and IgE in serum of mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells.Western blot was used to detect the expression of P-Ezrin and Ezrin in skin tissues.Results Celastrol significantly inhibited the swelling of ear and back skin tissues,reduced the de-granulation of inflammatory cells and mast cells,low-ered serum IgE and serum and lymph node levels of IL-4 and TNF-α,and reduced the activation of Ezrin in mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells was restored by the treat-ment with Ezrin siRNA.Conclusion Celastrol amel-iorates AD,which may be achieved by modulating Ezrin activation.
7.A nomogram for predicting residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compres-sion fractures
Jun-Ke LI ; Xu-Bin MA ; Liang LI ; Qing MA ; Xu-Dong WANG
China Journal of Orthopaedics and Traumatology 2024;37(6):553-559
Objective To construct percutaneous vertebroplasty for predicting osteoporotic vertebral compression fractures(OVCFs)nomogram of residual back pain(RBP)after percutaneous vertebroplasty(PVP).Methods Clinical data of 245 OVCFs patients who were performed PVP from January 2020 to December 2022 were retrospectively analyzed,including 47 males and 198 females,aged from 65 to 77 years old with an average of(71.47±9.03)years old,and were divided into RBP group and non-RBP group according to whether RBP occurred.Gender,age,comorbidities,fracture stage,body mass index(BMI),bone mineral density(BMD),visual analogue scale(VAS),Oswestry disability index(ODI)and other general infor-mation were collected;anterior vertebral height(AVH),anterior vertebral height ratio(AVH),anterior vertebral height ratio(AVHR),Cobb angle,intravertebral vacuum cleft(IVC),thoracolumbar fascia(TLF)injury,paravertebral muscle steatosis,injection volume and leakage of bone cement,bone cement dispersion pattern,anterior vertebral height recovery ratio(AVHRR),Cobb angle changes,etc.imaging parameters before operation and 24 h after operation were collected.Univariate analysis was performed to analysis above factors,and multivariate Logistic regression model was used to investigate indepen-dent risk factors for postoperative RBP,and Nomogram model was constructed and verified;receiver operating characteristic(ROC)curve and calibration curve were used to determine predictive performance and accuracy of the model,and Hosmer-Lemeshow(H-L)test was used for evaluation.The area under curve(AUC)of ROC was calculated,and Harrell consistency index(C index)was used to evaluate the predictive efficiency of model;decision curve analysis(DCA)was used to evaluate clinical practicability of model.Results There were 34 patients in RBP group and 211 patients in non-RBP group.There were no significant differences in gender,age,comorbidities,fracture stage,BMI,BMD,VAS,ODI,AVH,AVHR and Cobb angle be-tween two groups(P>0.05).Univariate analysis showed 6 patients occurred IVC in RBP group and 13 patients in non-RBP,the number of IVC in RBP group was higher than that in non-RBP group(x2=5.400,P=0.020);6 patients occuured TLF injury in RBP group and 11 patients in non-RBP group,the number of TLF injury in RBP group was higher than that in non-RBP group(x2=7.011,P=0.008);In RBP group,18 patients with grade 3 to 4 paraptebral steatosis and 41 patients in non-RBP group,RBP group was higher than non-RBP group(x2=21.618,P<0.001),and the proportion of bone cement mass in RBP group was higher than non-RBP group(x2=6.836,P=0.009).Multivariate Logistic regression analysis showed IVC(x2=4.974,P=0.025),TLF in-jury(x2=5.231,P=0.023),Goutallier grade of paravertebral steatosis>2(x2=15.124,P<0.001)and proportion of bone cement(x 2=4.168,P=0.038)were independent risk factors for RBP after PVP.ROC curve of model showed AUC of original model was 0.816[OR=2.862,95%CI(0.776,0.894),P<0.001].The internal verification of model through 200 bootstrap samples showed the value of C index was 0.936,and calibration curve showed predicted probability curve was close to actual probability curve.H-L goodness of fit test results were x2=5.796,P=0.670.DCA analysis results showed the decision curve was above None line and All line when the threshold value ranged from 6%to 71%.Conclusion IVC,TLF combined injury,paravertebral muscle steatosis with Goutallier grade>2,and bone cement diffusion with mass type are independent risk factors for RBP after PVP.The risk prediction model for RBP after PVP established has good predictive performance and good clinical practicability.
8.Comparison of the efficacy of LARS ligament and autogenous hamstring tendon plus high-strength suture in posterior cruciate ligament reconstruction
Gen LI ; Yu-Qi KE ; Liang YANG
China Journal of Orthopaedics and Traumatology 2024;37(7):641-648
Objective To compare the clinical efficacy of ligament advanced reinforcement system(LARS)and autoge-nous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL).Methods A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admit-ted to our hospital between August 2019 and December 2021 were selected for complete follow-up.There were 78 males and 18 females,40 cases of left leg and 56 cases of right leg,the aged from 20 to 56 years old with an average of(32.50±8.68)years old.The transplants were divided into two groups:LARS group(52 cases)and autogenous hamstring tendon plus high-strength suture group(44 cases).In the LARS group,there were 42 males and 10 females;with an average age of(31.84±8.62)years old;body mass index(BMI)was(24.73±2.29)kg·m-2;7 mm LARS was used to reconstruct PCL.In the autologous tendon group,there were 36 males and 8 females,with an average age of(33.06±8.99)years old,BMI was(23.52±2.16)kg·m-2,and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture.All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation,and subjective evaluation of knee function by Lysholm score,Tegner score,and International Knee Documentation Council(IKDC)score.Data from preoperative,3,6,and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients.Results Ninety-six patients were followed up for 12 months.KT-1000 measurement of knee joint in autoge-nous tendon group and LARS group before operation[(10.73±1.46)points vs(10.55±1.53)points],6 months after operation[(3.02±0.75)points vs(2.35±0.60)points],12 months after operation[(3.77±1.76)points vs(2.44±0.60)points].There was significant difference between the two groups at 6 and 12 months after operation(P<0.05),but there was no significant dif-ference between the two groups at 3 months after operation(P>0.05).In the autogenous tendon group and LARS group,before operation and 12 months after operation,total Lysholm score[(40.6±16.8),(91.25±6.35)points vs(51.92±18.52),(92.35±5.30)points],Tegner score[(1.8±0.7),(5.8±0.6)points vs(1.7±0.8)、(5.7±0.7)points]and total IKDC score[(54.50±6.33),(83.90±3.93)points vs(54.40±4.24),(83.62±3.64)points],the differences were statistically significant(P<0.05),indicating that the knee function of the two groups was improved after surgery.At 3 and 6 months after operation in the autoge-nous tendon group and LARS group,the total Lysholm score[(65.86±11.54),(74.60±6.46)points vs(73.46±6.42),(86.73±4.62)points],Tegner score[(2.5±0.6),(3.5±0.5)points vs(4.3±0.7),(5.0±1.4)points],the total scores of IKDC[(55.78±2.68),(70.62±4.74)points vs(65.31±4.60),(79.71±2.93)points].The difference between two groups was statistically sig-nificant(P<0.05).The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group.However,at 12 months after the operation,there was no significant difference in the score of knee joint function between the two groups(P>0.05).The results showed that the stability of LARS group was better than that of autologous tendon group.Conclusion Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability,with satisfactory postoperative results.Howervr the LARS provides superior postopera-tive stability.
9.Comparative study of total hip arthroplasty with and without femoral osteotomy in Crowe Ⅳ developmental dysplasia of the hip
Bo SUN ; Ke-Wei LI ; Ying-Zhou HOU ; Jin-Liang WANG ; Xuan WEI ; Shao-Hua WANG
China Journal of Orthopaedics and Traumatology 2024;37(10):972-977
Objective To compare the clinical effects of total hip arthroplasty(THA)with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH).Methods The data on 46 patients who underwent THA for unilateral Crowe ⅣDDH between 2012 and 2017 were analyzed retrospectively.They were divided into two groups according to the different surgical methods.There were 24 patients in the osteotomy group,3 males and 21 females,with an average age of(47.3±9.0)years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group,2 males and 20 females,with an average age of(51.6±8.3)years old ranged from 40 to 61 years old.The operative time,bleed loss,postoperative drainage volume,postoperative com-plications,ROM of hip,Harris hip score,limb length discrepancy(LLD),and radiological data were recorded.The femoral dislo-cation height and the implantation depth of sleeve were measured.Results All patients were followed up.The mean follow-up time was(3.8±1.2)years ranged from 2 to 6 years in the osteotomy group and(3.2±0.9)years ranged from 1 to 5 years in the non-os-teotomy group.The operative time(136.8±18.9)min,bleed loss(709.8±89.4)ml,postoperative drainage volume(308.8±98.2)ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min,(516.5±103.3)ml,(245.3±79.3)ml(P<0.05).The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups(P<0.05),but there was no significant difference between two groups(P>0.05).The LLD at last follow up was sig-nificantly increased compared with preoperative LLD in two groups,the LLD in non-osteotomy group(0.7±0.2)cm showed signif-cant smaller than the two osteotomy group(1.2±0.4)cm.Between osteotomy and non-osteotomy groups,the preoperative range of motion of hip joint[(89.5±19.7)°vs(102.5±16.8)°],the preoperative height of dislocation of femoral head[(4.56±0.61)cm vs(3.10±0.73)cm],the proximal implant depth of S-ROM[(0.93±0.36)cm vs(1.67±0.28)cm]was significantly different(P<0.05).Eleven patients in the osteotomy group still had claudication,and 4 patients in the non-osteotomy group had mild claudica-tion(P<0.05).In non-osteotomy group,3 patients developed nerve injury(1 patient of sciatic nerve,2 patients of femoral nerve)and 1 case developed periprosthetic fracture.In osteotomy group,2 case of dislocation and 2 cases of periprosthetic fractures.Conclusion Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD.However,osteotomy is more complex and time-consuming,limb length difference is greater,and the incidence of claudica-tion is higher.Furthermore,patients with smaller preoperative hip mobility,higher femoral dislocation,limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.
10.Analysis of 45 cases of early interruption of dual antiplatelet therapy after percutaneous coronary intervention
Wei-Zhe XIAO ; Chuan-Qiang WANG ; Yang YANG ; Ke CHEN ; Jing LIU ; Wen-Liang XIAO
Chinese Journal of Interventional Cardiology 2024;32(8):443-446
Objective To analyze the incidence of major adverse cardiovascular events(MACE)in 45 patients who unexpectedly interrupted dual antiplatelet therapy(DAPT)within one month after percutaneous coronary intervention(PCI).Methods A total of 4 876 patients who successfully underwent PCI and implanted one or more stents(excluding acute ST segment elevation myocardial infarction,drug coated balloon or non-drug coated ballooon only,and oral anticoagulants)between January 1,2017 and December 31,2022 were selected as the study subjects.A total of 45 patients with unexpected interruption of DAPT within one month after PCI were analyzed,and their clinical outcomes were followed up.Results Among the 45 patients,there were 29 males and 16 females,aged 48-80(61.7+15.3)years.The reasons for interrupting DAPT include:35 cases of bleeding;3 cases of malignant tumor surgery(including 2 bleeding patients);5 cases of trauma;2 cases of hematological diseases;2 cases of self-interruption of DAPT.6 patients who received low-molecular-weight heparin replacement therapy during the discontinuation period did not experience stent thrombosis or other MACE.Among the 39 patients without antithrombotic replacement therapy,5 developed stent thrombosis and acute myocardial infarction(5/45,11.1%).Except for 1 patient who voluntarily stopped DAPT 2 weeks after PCI,the remaining 4 cases were those who with concurrent bleeding within 2 weeks after PCI.DAPT was stopped for more than 10 days,and stent thrombosis occurred on the 10th,11th,11th,and 13th days after DAPT was stopped.Among the 4 patients,2 patients developed acute left heart failure and 1 patient died.Another case died due to brainstem hemorrhage.Conclusions Premature interruption of DAPT after PCI has a high potential risk.Patients who stop taking medication earlier,for a longer duration,and without replacement therapy have a higher risk.

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