In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective To establish a rapid high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the determination of linezolid and vancomycin in trace plasma/serum from pediatric patients with severe infection.Methods The plasma/serum specimens(10 μL)were precipitated by methanol,then the supernatant was injected for detection directly.The internal standards were linezolid-D3 and norvancomycin.The chromatographic separation was performed with gradient elution on a Kinetex? EVO C18 column(30.0 mm × 2.1 mm,2.6 μm)using water and acetonitrile,each containing 0.1％formic acid,as mobile phase.The flow rate was 0.5 mL·min-1 and column temperature was 40 ℃.The injection volume was 2 μL and the total run time was 2 min.For mass spectrometry,electrospray ionization source was chosen,positive ion monitoring was used with multi-reaction monitoring(MRM)mode.The selectivity,lower limit of quantification(LLOQ)& calibration curve,accuracy & precision,recovery,matrix effect,stability,cross detection of plasma and serum samples,evaluation of hemolytic and hyperlipidemic effect were investigated.Results The retention times of linezolid,vancomycin,internal standard linezolid-D3 and norvancomycin were 1.18,1.03,1.17 and 1.01 min,respectively.The calibration curves of linezolid and vancomycin were y=8.95 × 10-1x+3.49 × 10-3(r=0.997 1)and y=3.13 × 10-1x+6.93 × 10-2(r=0.997 4),with the linear ranges of 0.2-25.6 μg·mL-1 and 1-128 μg·mL-1,and the lower limits of quantification were 0.2 μg·mL-1 and 1 μg·mL-1,respectively.The intra-run and inter-run precisions relative standard deviation(RSD)were both less than 9.55％.The average extraction recoveries of the two drugs were 96.24％-104.57％.The RSDs of internal standards-normalized matrix effect were no more than 7.58％.Plasma and serum matrix samples could be cross-detected.The maximum tolerable hemolysis degree of linezolid and vancomycin were 2％and 5％,respectively,and the hyperlipidemic effect did not affect the quantitation.The stability of the samples was good under test conditions.This method was successfully applied to the analysis of plasma samples from 28 pediatric patients with severe infection in our hospital.Conclusion This assay is sample-saving,simple,rapid,accurate and robust,widely used,which can be applied to combination medication studies of linezolid and vancomycin and their therapeutic drug monitoring in pediatric patients.

Objective:To analyze the disease burden of kidney cancer, bladder cancer and prostate cancer and attributed risk factors in China from 1990 to 2019, and provide reference for the development of comprehensive prevention and control strategies.Methods:Based on the Global Burden of Disease Study 2019 platform, we collected the crude and age-standardized incidence rate, age-standardized mortality rate (ASMR), and disability-adjusted life year (DALY) of kidney cancer, bladder cancer and prostate cancer in China from 1990 to 2019. By using the log-linear regression model, trends were analyzed for overall and risk-attributable disease burden by calculating the average annual percentage change (AAPC).Results:From 1990 to 2019, the crude incidence rates of kidney cancer, bladder cancer and prostate cancer showed increasing trends in China, with an AAPC of 5.4% (95% CI: 4.9% - 5.9%), 4.1% (95% CI: 3.9% - 4.2%) and 5.6% (95% CI: 5.3% - 6.0%) (all P<0.001), respectively. Similar trends were found in age-standardized incidence rates with smaller AAPCs. For kidney cancer, the ASMR and age-standardized DALY rate significantly increased, with AAPC of 2.2% (95% CI: 1.5%-2.8%) and 1.5% (95% CI: 1.2%-1.9%) (all P<0.001), while the ASMR of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.7% - -0.5%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). The age-standardized DALY rate of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.8% - -0.4%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). Smoking was responsible for 48.2% of bladder cancer, 18.8% of kidney cancer and 9.8% of prostate cancer in total DALY. The age-standardized DALY rate of kidney cancer caused by smoking and high BMI showed an increasing trend, with AAPC of 3.0% (95% CI: 2.8%-3.2%) and 4.9% (95% CI: 4.7%-5.0%) (all P<0.001), and smoking-attributed age-standardized DALY rates of bladder cancer and prostate cancer decreased gradually with AAPC of -0.4% (95% CI: -0.6% - -0.2%) ( P<0.001) and -0.3% (95% CI: -0.4% - -0.1%) ( P=0.001). Conclusions:In the past 30 years, the disease burden of kidney cancer, bladder cancer and prostate cancer in China increased gradually, while the deaths and DALY of bladder cancer and prostate cancer decreased slightly. We should continue to strengthen the primary prevention strategies for smoking, obesity and other risk factors, and explore the appropriate screening tests and population-based screening strategies.

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.

Objective:To estimate the life expectancy gap and trends in China's provincial regions from 2000 to 2020,and to examine the socioeconomic factors contributing to the life expectancy gaps.Methods:The log-quadratic model was used to estimate life expectancy,and influencing factors were analyzed based on principal components analysis and regression analysis.Results:The findings of the study indicate a significant reduction in the gap of life expectancy at birth among China's provincial regions from 2000 to 2020.However,the gap in life expectancy for the elderly population is widening.Socioeconomic status factors,risk factors,and health service factors account for 71%,60%,and 43%of the gap in life expectancy among provinces,respectively,collectively explaining 74%.Conclusions and Suggestions:The current life expectancy gap between provincial regions in China remains substantial,determined by socioeconomic status factors,risk factors,and health service factors.However,it is worth noting that the impact of a healthy lifestyle as a mediating factor is not as significant as anticipated,suggesting that cultural and environmental factors also play a role in the regional health gap.It is recommended that,effective interventions such as healthy lifestyles should be implemented,and secondly,focus on the impact of cultural and health service factors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. Conclusion CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. Conclusions This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Outcome Assessment, Health Care ; Reference Standards ; Reproducibility of Results ; Research Design ; Clinical Trials as Topic