Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Objective To observe the influence of Qishen Yiqi Guttate Pills(mainly composed of Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,and Dalbergiae Odoriferae Lignum)on the clinical efficacy of patients with acute myocardial infarction after percutaneous coronary intervention(PCI).Methods Sixty post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type who met the inclusion criteria were randomly divided into a treatment group and a control group,with 30 patients in each group.The control group was treated with conventional western medicine,and the treatment group was treated with Qishen Yiqi Guttate Pills on the basis of treatment for the control group.The course of treatment for the two groups lasted for 3 months.The changes of cardiac function indicators and serum levels of hypersensitive C-reactive protein(hs-CRP)and N-terminal B-type natriuretic peptide precursor(NT-pro BNP)were observed before and after the treatment in the two groups,and the incidence of cardiovascular adverse events during the treatment in the two groups were also compared.Results(1)After treatment,the serum hs-CRP and NT-pro BNP levels of patients in the two groups were significantly decreased(P＜0.05)and the left ventricular ejection fraction(LVEF)was significantly increased(P＜0.05)compared with those before treatment.And the effects on lowering the levels of serum hs-CRP and NT-pro BNP and on increasing LVEF of the treatment group were significantly superior to those of the control group,the differences being statistically significant(P＜0.05).(2)During the treatment period,the incidence of cardiovascular adverse events in the treatment group was 6.67%(2/30),which was significantly lower than 26.67%(8/30)of the control group,and the difference was statistically significant when comparing the two groups(P＜0.05).Conclusion Qishen Yiqi Guttate Pills can effectively improve cardiac function,decrease serum hs-CRP and NT-pro BNP levels,and reduce the occurrence of adverse cardiovascular events in post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type.

Objective To explore the clinical efficacy of modified Xuefu Zhuyu Decoction combined with acupoint application for the treatment of patients with stable angina pectoris in coronary heart disease(SAP-CHD),and to evaluate its clinical value for the treatment of SAP-CHD.Methods A total of 92 patients with SAP-CHD of heart-blood stasis and obstruction complicated with qi deficiency type were randomly divided into control group and observation group,with 46 cases in each group.The control group was treated with conventional western medicine alone,and the observation group was treated with modified Xuefu Zhuyu Decoction combined with acupoint application on the basis of treatment for the control group.The two groups were treated for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Pittsburgh Sleep Quality Index(PSQI)scores,cardiac function indicators of left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD),and frequency and duration of angina pectoris in the two groups before and after treatment were observed.After treatment,the TCM syndrome efficacy in the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of TCM syndrome efficacy in the observation group was 91.30％(42/46),and that of the control group was 76.09％(35/46).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the scores of TCM syndromes in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.05).(3)After treatment,the PSQI scores of sleep quality in the two groups were lower than those before treatment(P＜0.05),and the decrease of PSQI score in the observation group was significantly superior to that in the control group after treatment(P＜0.05).(4)In terms of cardiac function,LVEF in the two groups after treatment was higher than that before treatment(P＜0.05),LVESD and LVEDD were lower than those before treatment(P＜0.05).The increase of LVEF and the decrease of LVESD and LVEDD in the observation group were significantly superior to those in the control group after treatment(P＜0.05).(5)After treatment,the frequency and duration of angina pectoris in the two groups were improved compared with those before treatment(P＜0.05),and the improvement in the frequency and duration of angina pectoris in the observation group was superior to that in the control group(P＜0.05).Conclusion On the basis of conventional western medicine treatment,modified Xuefu Zhuyu Decoction combined with acupoint application exerts certain clinical effect for the treatment of patients with stable angina pectoris in coronary heart disease.The combined therapy is effective on improving the cardiac function and sleep quality of the patients,reducing the attack of angina pectoris and shortening the duration of angina pectoris,with stronger efficacy than that of conventional western medicine alone.

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.
China ; Clinical Trials as Topic ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional ; Nonprescription Drugs/therapeutic use* ; Quality of Life ; Reproducibility of Results

The present study reviewed the clinical randomized controlled trials(RCTs) of Chinese patent medicine for pneumonia to provide references for clinical research, guideline development, and policy formulation, and promote the quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed were searched for RCTs of Chinese patent medicine for pneumonia from database inception to December 31, 2019. A total of 1 245 RCTs were included, involving 84 Chinese patent medicines, including 45 oral medicines and 39 injections. Specifically, 85.9% of RCTs had treatment course not exceeding 14 d; 43.3% of RCTs had a sample size of more than 100 cases and 6.1% of RCTs more than 200 cases; 13 types of interventions/controls were included in the RCTs, with Chinese patent medicine + western medicine vs western medicine as the top one used(32.6%). In outcome indicators, symptoms/signs(3 285) and physicochemical detection(2 066) were the most frequently applied. In the methodological evaluation, "allocation concealment" was not clearly described or mentioned in 71.2% of RCTs, and "blinding" in 23.9% of RCTs met the normative standards. Registration and research ethics were not clearly reported. There are many methodological deficiencies in terms of design and implementation in included RCTs, which may impact the reliability and practicability of the results of RCTs. Additionally, key standards were unclear(such as disease classification methods and selection of core outcome indicators). In conclusion, RCTs should give priority to the preciseness and scientificity of the protocol, strengthening quality control of the processes and accelerating the standardized research of key links.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Reproducibility of Results

The clinical randomized controlled trials(RCTs) of Chinese patent medicine in the treatment of chronic obstructive pulmonary disease(COPD) were reviewed and analyzed to provide references for clinical research, guideline development, policy formulation, and quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed, Cochrane Library, PubMed, EMbase were searched for RCTs of Chinese patent medicine for COPD as a source of clinical evidence from database inception to December 31, 2019. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. A total of 733 RCTs of Chinese patent medicine for COPD were included, among which 228 RCTs had a sample size higher than 100, accounting for 31.1% of total RCTs. Eighty-eight Chinese patent medicines were involved, including 40 oral medicines and 48 injections. A total of 327 RCTs mentioned intervention and control measures(Chinese patent medicine + conventional treatment vs conventional treatment), accounting for 43.0%. In addition, 94.40% of the RCTs reported the course of treatment, and 53.20% of the RCTs determined 8-14 d as the intervention course. The evaluation indicators adopted were numerous, among which physicochemical indicators(70.57%) and symptoms/signs(24.35%) were the most frequently employed. The operation of allocation concealment and blinding was not standard. Registration and the procedure related to ethics were mostly missing. The results indicate that there are prominent methodological problems in the clinical trials of Chinese patent medicine in the treatment of COPD, affecting the reliability and practicability of the trials. It is necessary to further standardize the design, implementation, and quality control of clinical trials of Chinese patent medicine in the treatment of COPD, highlight the clinical value of Chinese patent medicine for COPD, and improve the quality of evidence.
China ; Clinical Trials as Topic ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Reproducibility of Results

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.
Adult ; Heart-Assist Devices ; Humans ; Immunomodulation ; Male ; Middle Aged ; Myocarditis/therapy* ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*