1.Effect of Jiuxin Pill (救心丸)on Exercise Tolerance and Quality of Life in Patients of Stable Angina Pectoris:A Randomized,Double-Blind,Placebo-Controlled,Multi-Center Clinical Trial
Xianliang WANG ; Mingjun ZHU ; Daimei NI ; Jianguang WU ; Yitao XUE ; Chenglong WANG ; Xiaohua DAI ; Qian LIN ; Jun LI ; Zhiqiang ZHAO ; Shuai WANG ; Yingfei BI ; Tongzuo LIU ; Zhou ZHOU ; Jingyuan MAO
Journal of Traditional Chinese Medicine 2024;65(24):2549-2557
ObjectiveTo evaluate the effect and safety of Jiuxin Pill (救心丸) on exercise tolerance and quality of life in patients with stable angina pectoris (SAP). MethodsA randomised, double-blind, placebo-controlled, multicentre study design was used to enroll 170 patients of SAP from nine centres, which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan, and added Jiuxin Pill or placebo respectively, 2 pills (0.05 g) each time twicely for 28 days. The main outcomes were total exercise time (TED) in the exercise treadmill test and Seattle Angina Questionnaire (SAQ) scores including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP). The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min (HRR1), metabolic equivalents (METs), maximum magnitude of ST-segment depression, and the Borg rating of perceived exertion scale, the average number of angina attacks per week, withdrawal and reduction rate of nitroglycerin, traditional Chinese medicine syndrome scores, incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment, day 28±2 in treatment period, and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set (FAS) and safety analysis set (SS). Compared with the group before treatment and with the control group after treatment, the trial group had higher TED, HRR1, and METs, and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment (P<0.01). Compared with the group before treatment and with the control group after treatment and at follow-up, the total SAQ score and scores of AS, AF, TS and DP of the trial group after treatment and at follow-up elevated, while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced (P<0.01). There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups (P>0.05). Major adverse cardiovascular events occurred in 1 case (1/84, 1.19%) in the trial group and 1 case (1/85, 1.18%) in the control group, and the difference between groups was not statistically significant (P>0.05). A total of 3 cases of adverse events occurred in the trial group (3/84, 3.57%), and a total of 6 cases of adverse events occurred in the control group (6/85, 7.06%), and there was no statistically significant difference in the incidence of adverse events between groups (P>0.05). ConclusionIn the treatment of SAP, Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance, improve quality of life, and demonstrate great safety.
2.Effective Ingredients of Chinese Medicine in Prevention and Treatment of Osteoarthritis by Regulating Oxidative Stress: A Review
Shuang ZHANG ; Yingyan BI ; Xiaoting LIU ; Yusuo GONG ; Xuerui LIU ; Baohua YUAN ; Chenglong LU ; Xufan CHEN ; Ying WANG ; Jiaru GUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):282-289
Osteoarthritis (OA) is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA, with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope, multiple targets, and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species (ROS), relieve oxidative stress (OS) damage, and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde (MDA) and superoxide dismutase (SOD). Through the modulation of signaling pathways such as nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), NOD-like receptor protein 3 (NLRP3), and osteoprotegerin (OPG), they downregulated the expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), thereby effectively relieving local joint inflammation, protecting chondrocytes and bone tissue, inhibiting chondrocyte apoptosis, and further alleviating the progression of OA. Currently, there are still certain limitations in the medical research status and development trends of OA, necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA, providing new directions and ideas for future research.
3.The application of IVIM-DWI in evaluating the efficacy and prognosis of TACE using different embolization materials for hepatocellular carcinoma
Qinglong GUAN ; Haibo CHNE ; Chenglong LIU ; Gengfei CAO ; Haixiao ZHANG ; Chuanbao CUI
Journal of Interventional Radiology 2024;33(2):140-145
Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P<0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P<0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P<0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of<0.505×10-3 mm2/s and a postoperative D value of<0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.
4.False-positive HIV-1 nucleic acid testing results in patients with severe thalassemia after receiving cell and gene therapy
Yifan ZHONG ; Jifei NIU ; Yue LI ; Jing LIU ; Xiaohui WANG ; Hao LI ; Yongxia GAN ; Guilian LI ; Chenli ZHENG ; Chenglong LI ; Yifan CAI ; Zijie YANG ; Wei TAN ; Xiaozhen CHEN ; Tiejian FENG ; Cong JIN ; Jin ZHAO
Chinese Journal of Laboratory Medicine 2024;47(4):451-454
A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.
5.Survival analysis and compliance nomogram model construction of patients with non-small cell lung cancer over 65 years old after chemotherapy
Man ZHANG ; Peng SHEN ; Chenglong LI ; Yan LIU
Shanghai Journal of Preventive Medicine 2024;36(5):475-481
ObjectiveTo explore the risk factors and survival analysis of chemotherapy compliance in ≥65 years old patients with non-small cell lung cancer. MethodsFrom December 2018 to August 2020, 110 patients with non-small cell lung cancer ≥65 years old in our hospital were selected for study. According to their chemotherapy compliance, the patients were divided into untreated (25 cases), partial chemotherapy (30 cases) and full chemotherapy (55 cases). Multivariate Cox regression was used to analyze the independent risk factors affecting the compliance of chemotherapy among the three groups, and constructed a column chart prediction model and evaluated the diagnostic effectiveness of the model using receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves. The patients were followed up until August 2023. Kaplan-Meyer survival curve and Log-rank test were used to compare the differences in survival time between the groups. ResultsThere were significant differences among the three groups in gender, long-term smoking history, education level, Charlson complication index, toxic and side effects of chemotherapy drugs and dosage, pathological type, operation mode, place of residence, payment mode, chemotherapy stage, white blood cell count and neutrophils (P<0.05). Multivariate Cox analysis showed that patients' education level, pathological TNM stage, toxic and side effects of chemotherapy drugs and dosage, operation mode, residence, payment mode and chemotherapy stage were independent risk factors affecting chemotherapy compliance of patients with non-small cell lung cancer (all P<0.05). There were significant differences in the survival rates between the non-chemotherapy group and the full chemotherapy group, and between the partial chemotherapy group and the full chemotherapy group (P<0.05), but there was no significant difference between the non-chemotherapy group and the partial chemotherapy group (P>0.05). And based on this, a prediction model was constructed, and the ROC curve was drawn to show that the AUC of the model was 0.758 (95%CI: 0.743‒0.855), the sensitivity was 0.788, and the specificity was 0.853, indicating that the model had high discrimination, the calibration curve indicated that the prediction model had good accuracy, the clinical decision curve indicated that the predictive model had strong clinical practicality. ConclusionNSCLC tends to occur in the elderly. We should focus on the patients with low educational level, late pathological TNM stage, severe toxicity and side effects, high dose of chemotherapy drugs, having undergone open chest surgery, living in rural areas, without medical insurance, and in the period of chemotherapy consolidation and refractory relapse, so as to improve their compliance with chemotherapy.
6.Establishment and validation of the Sprague-Dawley rat model of osteoarthritis with kidney deficiency and blood stagnation
Cheng YANG ; Yusheng LI ; Hongzhuo JIAO ; Man SHANG ; Qi LIU ; Linzhen LI ; Fangyang FAN ; Chenglong ZHANG ; Xiaoyu ZHANG ; Juntao ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(27):4273-4280
BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.
7.Progress in regulation of JAK/STAT signaling pathway by traditional Chinese medicine in treatment of osteoarthritis
Xiaoting LIU ; Jiaru GUANG ; Yusuo GONG ; Baohua YUAN ; Chenglong LU ; Xufan CHEN ; Bifeng ZHANG
Chinese Journal of Pathophysiology 2024;40(2):375-384
Osteoarthritis(OA)mainly lies in the lesions of articular cartilage and surrounding tissues,pro-ducing osteophytes and bone sclerosis,resulting in damage to the articular cartilage.The main pathological mechanism of OA rests with a large number of inflammatory cytokines and inflammatory mediators produced by joint synovial lesions as well as pathological vascular growth at the junction of the synovium and cartilage,which may be one of the key reasons for promoting synovitis and cartilage damage.The OA mainly occurs in the knees,hips,hands and the spine.It is mainly manifested by chronic joint pain,swelling and stiffness,and limitation of motion seriously affects the functional activities of patients.The treatment of OA mainly relies on oral administration or intraarticular injection of drugs to relieve symp-toms.When OA develops to the middle and late stages,the action and life of patients will be seriously affected.There-fore,surgical replacement of joints is considered to ensure the basic life demands of patients.Studies show that traditional Chinese medicine(TCM)treatment has attracted widespread attention and application due to its unique advantages in pre-vention and treatment of OA.Janus kinase(JAK)/signaling transduction and transcriptional activator(STAT)signaling pathway may be one of the important signaling pathways that regulate the chondrocyte proliferation,differentiation and apoptosis.Moreover,it is closely associated with intra-articular inflammatory response.The JAK/STAT signaling pathway regulates the expression of inflammatory factors and related proteins through TCM so as to reduce the inflammatory re-sponse and decrease the chondrocyte damage.It has an important reference value for OA treatment.In this paper,the roles and mechanisms of the TCM monomers and active ingredients and the Chinese herbal compounds in OA by regulating JAK/STAT signaling pathway and affecting related cytokine and protein expression levels have been reviewed,providing a new method and direction for TCM treatment of OA.
8.Translocation of Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei mediates formation of multinucleated giant cells
Pan WU ; Chenglong RAO ; Dongqi NAN ; Jiangao CHEN ; Ziyuan ZHANG ; Wenzheng LIU ; Minyang WANG ; Jingmin YAN ; Qian LI ; Xuhu MAO
Journal of Army Medical University 2024;46(15):1721-1728
Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P<0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.
9.The diagnostic value of cone beam CT in styloid process syndrome via logistic regression combined with receiver operating characteristic curve analysis
Chenglong ZHOU ; Ruitao LI ; Yugang LIU ; Shubin LUO
Journal of Practical Radiology 2024;40(9):1417-1420
Objective To analyze the predictive value of cone beam computed tomography(CBCT)in styloid process syndrome(SPS)via logistic regression combined with receiver operating characteristic(ROC)curve.Methods A retrospective analysis was conducted on imaging data of 186 patients who underwent styloid CBCT.Among them,65 patients were clinically diagnosed with SPS(patient group),while 121 constituted the healthy controls(control group).The styloid length,inclination angle,and anteversion angle were measured,respectively.Logistic regression analysis was employed,and ROC curves were plotted to calculate sensitivity,specificity,and Youden index,the diagnostic cut-off values for SPS was obtained.Results In the control group,the styloid length was(29.66±7.22)mm,inclination angle was(22.34±3.05)°,and anteversion angle was(31.01±4.13)°.In the patient group,the styloid length was(40.30±8.65)mm,inclination angle was(21.86±3.74)°,and anteversion angle was(35.88±6.37)°.Logistic regression analysis revealed that styloid length and anteversion angle were risk factors for diagnosing SPS(P<0.05),while inclination angle was not a risk factor for diagno-sing SPS(P>0.05).ROC curve analysis demonstrated that diagnosing SPS,the area under the curve(AUC),sensitivity,specificity,and optimal cut-off value for styloid length were 0.868,92.3%,69.7%,and 31.23 mm,respectively;and for anteversion angle were 0.765,63.1%,89.3%,and 35.15°,respectively.Conclusion CBCT measurements of styloid length,inclination angle,and antever-sion angle suggest that a styloid length exceeding 31.23 mm and an styloid anteversion angle greater than 35.15° may indicate a higher likelihood of SPS.CBCT is a convenient,cost-effective,and safe diagnostic tool with positive clinical implications.
10.Association between the 24-hour movement behaviors and executive function in preschoolers
Chenglong WANG ; Huiqi SONG ; Mingzhe LI ; Yongsong LIU ; Jingjing WANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(8):720-726
Objective:To explore the characteristics of 24-hour movement in preschoolers and its relationship with executive function.Methods:The study subjects consisted of 555 preschoolers in Zhuhai City. An objective measurement approach was employed, physical activity level was assessed by utilizing accelerometers and executive function was evaluated by computerized behavioral tests.The characteristics of 24-hour movement in children were described.Data were analyzed using SPSS 26.0 software, independent samples t-test was used to compare differences in 24-hour activity behaviors across genders, and multivariate linear regression was used to explore the effect of preschoolers' achievement of activity behaviors on executive functioning. Results:According to the physical activity guideline for Chinese preschoolers aged 3-6 years recommendations for children's daily moderate to vigorous-intensity physical activity, sedentary screen time, and sleep duration, among the study participants, the compliance rate of moderate to vigorous-intensity physical activity (≥60 min/d) was 33.9 %(188/555), sedentary screen time (≤1 h/d) was 43.4%(241/555), and sleep duration (10-13 h/d) was 83.4 %(463/555). Only 13.3 %(74/555) of the participants met the recommended guidelines for all three behaviors. The correct score of the working memory test was (60.6±20.3) and the reaction time of the inhibitory control test was (695.1±135.8) ms. In male preschoolers, moderate to vigorous-intensity physical activity (≥60 min/d) positively predicted working memory( β=0.121, P=0.037), while sedentary screen time (≤1 h/d) negatively predicted inhibitory control ( β=-0.122, P=0.036). Conclusions:The daily compliance rate of moderate to vigorous-intensity physical activity and sedentary screen time is low among preschooler. The former is positively correlated with working memory in preschool boys, while the latter is negatively correlated with inhibitory control.

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