1.Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Ulcerative Colitis
Yasheng DENG ; Lanfang MAO ; Jiang LIN ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinzhong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):245-251
To systematically review randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) intervention in ulcerative colitis (UC), and analyze the characteristics of these studies and their outcome indicators, thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed, and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included, with a sample size of 44 853 participants. The largest sample size was 218 cases, and the smallest was 28 cases, with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types, the top three were large intestine dampness-heat syndrome (31.05%), spleen and kidney yang deficiency syndrome (12.47%), and spleen deficiency with dampness syndrome (9.17%). The interventions, ranked by frequency of use, included internal Chinese medicine compounds/preparations (64.5%), Chinese medicine compounds/preparations with retained enema (18.2%), internal Chinese medicine compounds/preparations + external TCM treatment (5.95%), and external TCM treatment alone (4.86%). The treatment duration was mainly 4-8 weeks (64.86%), with 61 studies (10.99%) reporting follow-up time. A total of 157 outcome indicators were used, with a frequency of 3 460 occurrences, classified into six domains: TCM syndromes and symptoms (346 occurrences, 10%), symptoms/signs (541 occurrences, 15.64%), physical and chemical examinations (2 119 occurrences, 61.24%), quality of life (107 occurrences, 3.09%), long-term prognosis (61 occurrences, 1.76%), and safety events (284 occurrences, 8.21%). The analysis reveals several limitations in the outcome indicators of TCM intervention in UC, including the lack of a basis for sample size calculation, non-standardized TCM syndrome classification, absence of trial design and registration, inadequate blinding and allocation concealment, adherence issues with interventions, imbalanced selection of surrogate and endpoint indicators, inconsistency in the timing of outcome measurements, design issues that require standardization, and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification, clear efficacy evaluation indicators, key endpoint indicators, and reasonable measurement time points. Long-term prognostic impacts, comprehensive assessments of patients' quality of life, and consideration of economic benefits should be emphasized, providing a basis for the clinical practice of TCM in the treatment of UC.
2.Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Ulcerative Colitis
Yasheng DENG ; Lanfang MAO ; Jiang LIN ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinzhong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):245-251
To systematically review randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) intervention in ulcerative colitis (UC), and analyze the characteristics of these studies and their outcome indicators, thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed, and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included, with a sample size of 44 853 participants. The largest sample size was 218 cases, and the smallest was 28 cases, with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types, the top three were large intestine dampness-heat syndrome (31.05%), spleen and kidney yang deficiency syndrome (12.47%), and spleen deficiency with dampness syndrome (9.17%). The interventions, ranked by frequency of use, included internal Chinese medicine compounds/preparations (64.5%), Chinese medicine compounds/preparations with retained enema (18.2%), internal Chinese medicine compounds/preparations + external TCM treatment (5.95%), and external TCM treatment alone (4.86%). The treatment duration was mainly 4-8 weeks (64.86%), with 61 studies (10.99%) reporting follow-up time. A total of 157 outcome indicators were used, with a frequency of 3 460 occurrences, classified into six domains: TCM syndromes and symptoms (346 occurrences, 10%), symptoms/signs (541 occurrences, 15.64%), physical and chemical examinations (2 119 occurrences, 61.24%), quality of life (107 occurrences, 3.09%), long-term prognosis (61 occurrences, 1.76%), and safety events (284 occurrences, 8.21%). The analysis reveals several limitations in the outcome indicators of TCM intervention in UC, including the lack of a basis for sample size calculation, non-standardized TCM syndrome classification, absence of trial design and registration, inadequate blinding and allocation concealment, adherence issues with interventions, imbalanced selection of surrogate and endpoint indicators, inconsistency in the timing of outcome measurements, design issues that require standardization, and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification, clear efficacy evaluation indicators, key endpoint indicators, and reasonable measurement time points. Long-term prognostic impacts, comprehensive assessments of patients' quality of life, and consideration of economic benefits should be emphasized, providing a basis for the clinical practice of TCM in the treatment of UC.
3.Effect of pegylated interferon-α-2b therapy on cytotoxicity of virus-specific CD8+ T cells in HBeAg-negative patients with chronic hepatitis B virus infection
Lei QIN ; Guangpeng LI ; Peijun SHEN ; Lanfang ZHANG ; Xiaofei YANG ; Meijuan PENG ; Ye ZHANG
Journal of Clinical Hepatology 2025;41(4):628-636
ObjectiveTo investigate the change in the activity of hepatitis B virus (HBV)-specific CD8+ T cells after pegylated interferon-α-2b (PEG-IFN-α-2b) therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b (180 μg/week, subcutaneous injection) antiviral therapy. The study endpoint was HBsAg clearance (course of treatment<48 weeks) or 48 weeks (course of treatment≥48 weeks). Peripheral blood mononuclear cells were isolated at baseline and study endpoint, and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ. A total of 17 HLA-A*02-restricted patients were selected, and CD8+ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8+ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells, and the levels of HBV DNA, cytotoxic molecules, and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands, and the cytotoxicity of HBV-specific CD8+ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% (16/53). There were no significant differences in peripheral blood T cell counts (CD3+, CD4+, and CD8+ T cells) between baseline and study endpoint (P>0.05). At study endpoint, there was a significant increase in the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ (U=177.50, t=11.90, U=186.50, all P<0.001), and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8+ T cells than those without HBsAg clearance (U=120.50, t=2.73, U=121.50, all P<0.01). In the direct- and indirect-contact co-culture systems at study endpoint, HBV-specific CD8+ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells (all P<0.001) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (all P<0.05); in the direct-contact co-culture system, HBV-specific CD8+ T cells induced significant increases in the mortality rate of HepG2.2.15 cells (13.62%±3.27% vs 11.39%±2.40%, t=2.27, P=0.030) and the secretion of perforin and granzyme B (t=72.50, U=52.50, both P<0.05). In the direct- and indirect-contact co-culture systems, compared with HBV-specific CD8+ T cells from the patients without HBsAg clearance, the HBV-specific CD8+ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA (P<0.05) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (P<0.05). ConclusionPEG-IFN-α-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection, and the activity of HBV-specific CD8+ T cells is significantly enhanced, which is closely associated with HBsAg clearance.
4.Improvement effect and mechanism of Shengmai powder on heart failure mice with qi-yin deficiency
Lanfang KANG ; Jian LI ; Yating ZHAO ; Yingchun CHEN ; Guiyin CHEN ; Xiaobo NIE ; Jiao LIU ; Jie CHENG
China Pharmacy 2025;36(17):2127-2133
OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure (HF) mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group (water), model group (water), Shengmai powder low-, medium-, and high-dose groups [2.61, 5.22 and 10.44 g/kg (based on crude drug dosage)] and positive control group (metoprolol, 30 mg/kg), with 10 mice in each group. Except for the blank group, all other groups were subcutaneously injected with D-galactose, and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling, the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine (TCM) syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action, the percentage of immobility time, and the swimming exhaustion time of mice. The contents of aspartate transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) in the serum of mice were detected; cardiac function indexes [heart rate, left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular mass index and whole heart mass index] were all detected; the histopathological morphology of mice myocardium was observed; the level of cardiomyocyte apoptosis in mice was detected; mRNA expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and Cleaved-caspase-3 in myocardial tissue of mice were detected; the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 (RyR2) and phospholamban (PLB)] in myocardial tissue of mice were detected. RESULTS Compared with the blank group, the body weight, total distance of open field action, swimming exhaustion time, LVEF, LVEDD, Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened (P<0.05); TCM syndrome score, the percentage of immobility time, heart rate, LVESD, left ventricular mass index, whole heart mass index, cardiomyocyte apoptosis rate, the contents of CK, LDH and AST in serum, mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased (P<0.05); there were inflammatory cell infiltration, disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder, most of the above quantitative indexes in mice were significantly reversed (P<0.05), the inflammatory cell infiltration in myocardial tissue was reduced, and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function, reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.
5.Unveiling the renoprotective mechanisms of self-assembled herbal nanoparticles from Scutellaria barbata and Scleromitrion diffusum in acute kidney injury: A nano-TCM approach.
Lunyue XIA ; Qunfang YANG ; Kangzhe FU ; Yutong YANG ; Kaiyue DING ; Yuexue HUO ; Lanfang ZHANG ; Yunong LI ; Borong ZHU ; Peiyu LI ; Yijie HUO ; Liang SUN ; Ya LIU ; Haigang ZHANG ; Tao LIU ; Wenjun SHAN ; Lin ZHANG
Acta Pharmaceutica Sinica B 2025;15(8):4265-4284
Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.
7.Differential Analysis of Erythrocyte Flexibility of PbK173 Artemisinin-sensitive Strains
Hongying ZHOU ; Wenhui XU ; Miyi YANG ; Hang SHI ; Lanfang LI ; Guihua YU ; Canghai LI ; Huajing WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):95-103
ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 (PbK173)-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free (SPF) male C57BL/6 mice were randomly divided into three groups, with 30 mice each in the control group and PbK173-resistant (PbK173-R) group, and 42 mice in the PbK173-sensitive (PbK173-S) group. Except for the control group, the rest groups were vaccinated with 1×107 PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods (control group, PbK173-R/PbK173-S), dihydroartemisinin (DHA, 40 mg·kg-1) and malaridine (MD, 6 mg·kg-1) were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration (dosing period) and on the fifth day at the end of administration (recovery period), and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods, there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period, there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However, during the recovery period, the red blood cell count, hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group (P<0.05) in the MD group. Compared with that of the control group, the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced (P<0.01), and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group (P<0.01). The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period (P<0.01). The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period (P<0.05). Compared with those in the control group, the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced (P<0.01). Compared with those in the PbK173-R group, the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane, and the erythrocyte flexibility exhibited a decreasing trend in the following order: normal group, PbK173-R group, and PbK173-S group.
8.The regulatory effect of interleukin-33 signaling pathway on monocytes in patients with hepatitis B virus-associated hepatocellular carcinoma
Lu YANG ; Lanfang ZHANG ; Lijun MENG ; Yanli ZHU ; Jun KUAI ; Wenjing LI
Immunological Journal 2024;40(2):151-159
To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.
9.Progress in the diagnosis and treatment of reactive arthritis in children
Huizhen LI ; Jinping XU ; Lanfang CAO
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):469-472
Reactive arthritis(ReA) is a kind of sterile, non-purulent arthritis that occurs after microbial infections far from the joints.The disease has a broad spectrum, and it can be classified into three categories based on clinical characteristics: human leukocyte antigen B27(HLA-B27)-associated ReA, acute rheumatic fever(ARF), and post-streptococcal reactive arthritis(PSRA).In addition to joints, it may also involve the gastrointestinal tract, skin, eyes, and heart.Unlike adults, the pathogenesis of ReA in children is more complex.HLA-B27-associated ReA is more common after gastrointestinal and respiratory infections, with less involvement of the central axis and sacroiliac joints and more involvement of the hip and peripheral joints and attachment point inflammation.ARF is most common in children aged 5 to 15 years, characterized by migratory and multiple arthritis.The duration of onset of PSRA in children is shorter than that in adults.This article reviews the epidemiology, clinical manifestations, diagnosis and treatment of ReA in children to improve clinicians′ understanding of ReA in children.
10.Interpretation of clinical practice guidelines for juvenile idiopathic arthritis associated uveitis
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):576-578
Juvenile idiopathic arthritis associated uveitis (JIA-U) is a primary extra-articular complication of juvenile idiopathic arthritis, which can cause symptoms such as red eyes, eye pain, photophobia, floating shadows in front of the eyes, or decreased vision.In severe cases, it can induce blindness and cause significant harm to children and their families.The American College of Rheumatology, the Multinational Interdisciplinary Working Group for Uveitis in Childhood, the Pediatric Rheumatology European Society and the Canadian Rheumatology Association have released relevant clinical guidelines and expert consensus on this disease.This article mainly interprets the above-mentioned clinical guidelines and expert consensus regarding the diagnosis, treatment, and long-term management of JIA-U, to improve the efficiency and management quality in clinically diagnosing and treating JIA-U.

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