BackgroundThe incidence of chronic kidney disease (CKD) is increasing yearly; however, an effective drug treatment method for early-stage CKD (stage G3) is lacking. Thus, we aimed to determine the efficacy and safety of Guben Tongluo formula (GTF) for patients with CKD (stage G3).MethodsOne hundred and twenty participants were enrolled and randomly divided into losartan potassium (LP) group and LP + GTF group. LP group received general treatments combined with LP, and LP + GTF group received general treatments combined with GTF and LP. Evaluation indicators included changes in renal function, serum lipid, inflammatory factors, oxidative damage, renal fibrosis, traditional Chinese medicine (TCM) symptom scores, and clinical effective rate. In addition, vital sign indicators and adverse events (AEs) were closely observed throughout the study.ResultsScr and BUN levels were significantly lower and eGFR were significantly improved in LP + GTF group (p < 0.05). There was no statistically significant difference of UA and 24 h U-pro levels (p > 0.05). TG, TC levels were significantly lower and HDL-C levels were significantly higher in LP + GTF group (p < 0.01). No statistically significant difference in LDL-C levels was observed (p > 0.05). Inflammatory factors levels were significantly lower in LP + GTF group (p < 0.01). Notable increases in HO-1 and SOD levels were observed in LP + GTF group (p < 0.01), and MDA levels showed no statistically significant difference (p > 0.05). CTGF and TGF-β1levels were significantly lower in LP + GTF group (p < 0.01), while no significant difference was observed of PC-III and Col-IV levels (p > 0.05). TCM syndrome scores in LP + GTF group were significantly lower (p < 0.01). The clinical efficiency rate in LP + GTF group (73.3%) was better than that in LP group (40%). No significant between-group differences were observed in AEs.ConclusionLP + GTF group demonstrated a better clinical efficacy rate than LP group. GTF regulates serum lipid levels and has anti-inflammatory, antioxidative, and anti-renal fibrosis effects. GTF showed potential benefits in this small multicenter randomized controlled trial, warranting confirmation in larger, fully blinded randomized trials.

Acute kidney injury (AKI) represents significant medical challenges due to its elevated rates of morbidity and mortality, with limited therapeutic options currently available. Hence, the exploration of novel medicinal treatments for AKI management remains vital. Substances of medicine food homology (SMFH), referring to substances having characteristics of both food and medicine, have been applied in China for thousands years.They could be used for daily diets and body conditioning. Traditional Chinese medicine (TCM), with its naturally derived components and demonstrated effectiveness, presents distinctive benefits in AKI treatment. Numerous studies have shown that SMFH and TCM phytochemicals could function satisfactorily with nephroprotective effects and have a significant effect on alleviating AKI as well as its complications. In this review, the pathogenesis of AKI was illustrated. We concentrated on SMFH and TCM phytochemicals against AKI and tried to summarize the underlying mechanisms in various kinds of AKI, highlighting the crucial phytochemical components in AKI prevention and therapy. Besides, strategies for SMFH and TCM phytochemicals globalization are analysed. This review comprehensively reveals that SMFH and TCM phytochemicals exhibit promising potential for AKI intervention by targeting various signal pathways and targets, which would contribute to AKI's cognition, preventive treatments, as well as global promotion.

BackgroundDiabetic retinopathy, a prevalent complication of diabetes mellitus, is a growing public health concern. The use of robust predictive models can aid healthcare professionals in identifying high-risk patients, enabling them to implement early intervention and treatment strategies.ObjectiveTo systematically evaluate published prediction models for diabetic retinopathy, select better prediction models for healthcare professionals, and provide a valuable reference for model optimization.MethodsA comprehensive search was conducted across the PubMed, Web of Science, Embase, and the Cochrane Library databases for relevant literature on predictive models for diabetic retinopathy. The search period was set from the time of library construction to November 14, 2023. Furthermore, risk of bias and applicability assessment of the included study models were performed using the PROBAST risk assessment tool.ResultsA total of 2030 studies were retrieved, including 15 studies. The range of the working characteristic curve of the subjects for the 15 models varied from 0.700 to 0.960. All 15 included studies were recognized as high risk of bias. However, five studies had better applicability. The 15 models had Common risk factors for the 15 models included diabetes duration, age, glycosylated hemoglobin, serum creatinine and urinary albumin creatinine ratio.ConclusionsWhile the performance of the 15 models had certain predictive performance, the high risk of bias is a concern. Hopefully, future studies will ensure transparency and science in the model-building process by conducting large-sample integrated machine learning, reinforcing multicenter external validation. This study was registered with PROSPERO, an international prospective systematic evaluation registry platform, and the title was approved with registration number CRD42023483749.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024559392.

Adropin is a secreted peptide encoded by the energy homeostasis‑associated gene, which also functions as a membrane‑bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non‑alcoholic fatty liver disease/non‑alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.

ObjectiveTo investigate the potential diagnostic and prognostic implications of inflammatory cytokine levels in the cerebrospinal fluid (CSF) of patients with spontaneous intracerebral hemorrhage (SICH) upon their initial hospital admission.MethodsOur cohort included 100 patients diagnosed with acute SICH, presenting to the Department of Neurosurgery. Additionally, we recruited 50 individuals without central nervous system (CNS) pathology, treated concurrently at our facility, as controls. CSF samples, collected upon hospital entry, were quantitatively assessed for 10 inflammatory cytokines using the Mesoscale Discovery Platform (MSD, Rockville, MD, USA) electrochemiluminescence technology, followed by validation through enzyme-linked immunosorbent assay (ELISA).ResultsWe observed a marked elevation of IL-6, IL-8, IL-10, and TNF-alpha in the CSF of the SICH subgroup compared to controls. Higher Glasgow Coma Scale (GCS) scores in SICH patients corresponded with lower CSF concentrations of IL-6, IL-8, IL-10, and TNF-alpha, indicating an inverse relationship. Notably, CSF inflammatory cytokine levels were consistently higher in SICH patients with hydrocephalus than in those without. Increases in IL-6, IL-8, IL-10, and TNF-alpha in the CSF were notably more pronounced in the poor prognosis group (Glasgow Outcome Scale, GOS 1-3) compared to those with a favorable prognosis (GOS 4-5). The AUC values for these cytokines in predicting SICH prognosis were 0.750, 0.728, 0.717, and 0.743, respectively.ConclusionsInitial CSF levels of IL-6, IL-8, IL-10, and TNF-alpha upon admission provide significant insights into the severity of neural damage and are robust indicators for prognosis in SICH patients.

ObjectiveThis study aims to conduct a detailed bibliometric and visual analysis of acute kidney injury (AKI) and immune-related research conducted over the past two decades, focusing on identifying emerging trends and key areas of interest.MethodsThe Web of Science Core Collection (WoSCC) was utilised for the meticulous examination of various parameters including publication volume, authorship, geographic distribution, institutional contributions, journal sources, prevalent keywords and citation frequencies. Data were intricately visualised and interpreted using VOSviewer, CiteSpace and Excel 365 software.ResultsAnalysis of the WoSCC database revealed 3,537 articles on AKI and immunisation, originating from 94 countries and regions, involving 3,552 institutions and authored by 18,243 individuals. Notably, the top five countries contributing to this field were the United States, China, Germany, Italy and the United Kingdom, with the United States leading with 35.76% of total publications. Among the 3,552 contributing institutions, those in the United States were predominant, with Harvard University leading with 134 papers and 3,906 citations. Key journals driving productivity included Frontiers in Immunology, Kidney International, Journal of the American Society of Nephrology and International Journal of Molecular Sciences, with Kidney International being the most cited, followed by Journal of the American Society of Nephrology and New England Journal of Medicine. Prominent authors in the field included Ronco Claudio, Okusa Mark D and Anders, Hans-Joachim. Co-citation clustering and timeline analysis highlighted recent research foci such as COVID-19, immune checkpoint inhibitors, regulated necrosis, cirrhosis and AKI. Keyword analysis identified “inflammation,” “ischaemia-reperfusion injury,” “sepsis,” “covid-19,” and “oxidative stress” as prevalent terms.ConclusionThis study provides the first bibliometric analysis of AKI and immune research, offering a comprehensive overview of research hotspots and evolving trends within the field.

ObjectiveThis study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis. Methods98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis. ResultsThe total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p < 0.05). Scr, BUN, and UA levels decreased while eGFR levels increased in both groups (p < 0.05), with a greater magnitude of change observed in the RG + CHF group. Urinary AKI biomarkers decreased more in RG + CHF group (p < 0.05). No serious adverse events occurred during the trial. 58 different lipid metabolites and 48 lipid biomarkers were identified. According to the KEGG database, the possible metabolic pathways involved triglyceride metabolic pathway and fat digestion and absorption metabolic pathways. ConclusionCHF-II effectively alleviated kidney injury and improved TCM syndrome scores in patients with A on C. Lipid differential metabolites could serve as diagnostic indicators for AKI in patients with CKD. The possible metabolic pathways might be implicated in therapeutic action of CHF-II in the prevention and treatment of patients with A on C.

ABSTRACT Background: The gut microbiota is closely associated with chronic kidney disease (CKD) development and prognosis. However, a comprehensive understanding of publication trends and research focuses within this domain remains limited. This study aimed to elucidate the relationship between the gut microbiota and CKD through a bibliometric analysis. Methods: Literature published between 2001 and 2022 on gut microbiota and CKD was obtained from the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer and CiteSpace were used to analyze research trends in this area. Results: We extracted 758 articles for further analysis. China ranked first with 240 published documents, followed by the USA with 211. However, the USA ranked first regarding citation frequency with 11,380 citations, while China ranked second. The University of California Irvine and Kidney International emerged as the leading institution and journal, respectively, with the former leading in document production and citations. Although Kidney International featured fewer documents than other journals, it exhibited the highest citation count. The keywords representing the research interests mainly included: (1) gut microbiota influences the development of CKD, (2) application of probiotics in the treatment of CKD, and (3) potential mechanism of gut microbiota in CKD. Conclusion: Our analysis indicates significant advancements in understanding the association between gut microbiota and CKD. It also provides a comprehensive overview of publication trends, research hotspots, and frontiers, which may provide guidelines for future research.

Objectives: To evaluate whether novel biomarkers of renal injury, serum HE4 and NT-proBNP could predict acute kidney injury (AKI) on chronic kidney disease (CKD) (A on C) and assess the specificity and efficiency of serum creatinine (SCr), HE4 and NT-proBNP in identifying potential AKI. Meanwhile, the potential early-warning value of HE4 and NT-proBNP in CKD patients was explored.Methods: We performed a single-center, retrospective cohort study of 187 adult CKD patients. 32 AKI (grades 1–2) patients with pre-existing CKD (stages 3–5) were Group 1, 59 patients of CKD (stages 4–5) were Group 2. Another 96 patients of CKD (stages 1–3) were Group 3. All patients received general treatments, Group 1 patients received Chinese herb formulation (Chuan Huang Fang-Ⅱ, CHF-Ⅱ) simultaneously. These 155 CKD (stages 1–5) without AKI patients were observed for descriptive analysis.Results: HE4 in Group 1 (860.63 ± 385.40) was higher than that in Group 2 (673.86 ± 283.58) before treatments. BUN, SCr, UA, NGAL, IL18, HE4 and NT-proBNP in Group 1 were lower, while eGFR was higher (p < 0.01, after vs. before treatments). In Group 1, both HE4 and NT-proBNP were positively correlated with SCr (respectively r = 0.549, 0.464) before treatments. The diagnostic performance of serum HE4 and NT-proBNP for A on C was 351.5 pmol/L, 274.5 pg/mL as the optimal cutoff value Area Under Curve (AUC) 0.860 (95% CI: 0.808 – 0.913, p < 0.001), [AUC 0.775 (95% CI: 0.697 – 0.853, p < 0.001), with a sensitivity and specificity of 100% and 66.5%, 87.5% and 48.8%, respectively]. In Group 2, serum HE4 was correlated with SCr (r = 0.682, p < 0.01) before treatments. Serum HE4 and NT-proBNP were elevated in advanced CKD stages, and were increased as CKD stages progressed with statistical significance.Conclusion: This work indicated serum HE4 and NT-proBNP should elevate in A on C and CKD patients, HE4 is positively correlated with the disease severity, and patients with higher HE4 and NT-proBNP usually have poorer prognosis. Thus, serum HE4 and NT-proBNP are impactful predictors of A on C. Additionally, serum HE4 and NT-proBNP have the potential to evaluate clinical efficacy of A on C.

Lower limb microcirculatory ischemic disease is a vascular disorder primarily characterized by limb pain, gangrene, and potential amputation. It can be caused by various factors, such as hyperglycemia, atherosclerosis, and infection. Due to the extremely narrow luminal diameter in lower limb microcirculatory ischemic lesions, both surgical and medical interventions face challenges in achieving satisfactory therapeutic outcomes within the microvessels. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) exhibit promising potential in the treatment of microcirculation ischemic lesions due to their small size and ability to promote angiogenesis. After undergoing substantial losses during the process of EVs transportation, only a minimal fraction of EVs can effectively reach the site of microcirculatory lesions, thereby compromising the therapeutic efficacy for microcirculatory disorders. Herein, an ultrasound-responsive system utilizing 2-(dimethylamino)ethyl methacrylate-b-2-tetrahydropyranyl methacrylate (DMAEMA-b-THPMA) micelles to encapsulate MSCs-EVs has been successfully constructed, with the aim of achieving localized and targeted release of EVs at the site of microcirculatory lesions. The reversible addition-fragmentation chain transfer (RAFT) polymerization method facilitates the successful synthesis of diblock copolymers comprising monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA) and monomer 2-tetrahydropyranyl methacrylate (THPMA). The DMAEMA-b-THPMA micelles exhibit a nanoscale structure, reliable biocompatibility, ultrasound responsiveness, and conspicuous protection of EVs. Furthermore, the implementation of low-energy-density ultrasound can enhance angiogenesis by upregulating the levels of the vascular endothelial growth factor (VEGF). In in vivo experiments, the ultrasound-responsive system of the DMAEMA-b-THPMA micelles and MSCs-EVs synergistically enhances therapeutic efficacy by promoting angiogenesis, improving vascular permeability, and optimizing vascular. In conclusion, this work demonstrates bioapplication of an ultrasound-responsive micellar nanosystem loaded with EVs for the treatment of lower limb microcirculatory ischemic disorders.

Abstract Drug-induced nephrotoxicity is a common cause of acute kidney injury (AKI), and drug-induced AKI (DI-AKI) is becoming a serious public health concern. DI-AKI can be triggered by multiple drugs, alone or in combination. The incidence, pathological mechanisms, and risk factors of DI-AKI are largely unknown. Thus, there is a need for greater monitoring of DI-AKI to reduce the risks of serious complications and other hazards related to DI-AKI. This review summarizes the epidemiology of DI-AKI, along with its potential pathogenesis, associated drugs, independent risk factors, and possible early biomarkers. Additionally, because certain traditional Chinese medicine (TCM) prescriptions and their components have been reported to prevent and treat some types of DI-AKI (e.g., contrast-induced AKI), this review summarizes TCM methods for the prevention and treatment of DI-AKI.

Background The amygdala plays a crucial role in the central pathogenesis mechanism of primary dysmenorrhea (PDM). However, the detailed pain modulation principles of the amygdala in PDM remain unclear. Here, we applied the Granger causality analysis (GCA) to investigate the directional effective connectivity (EC) alterations in the amygdala network of PDM patients. Methods Thirty-seven patients with PDM and 38 healthy controls were enrolled in this study and underwent resting-state functional magnetic resonance imaging scans during the pain-free stage. GCA was employed to explore the amygdala-based EC network alteration in PDM. A multivariate pattern analysis (MVPA)-based machine learning approach was used to explore whether the altered amygdala EC could serve as an fMRI-based marker for classifying PDM and HC participants. Results Compared to the healthy control group, patients with PDM showed significantly decreased EC from the amygdala to the right superior frontal gyrus (SFG), right superior parietal lobe/middle occipital gyrus, and left middle cingulate cortex, whereas increased EC was found from the amygdala to the bilateral medial orbitofrontal cortex. In addition, increased EC was found from the bilateral SFG to the amygdala, and decreased EC was found from the medial orbitofrontal cortex, caudate nucleus to the amygdala. The increased EC from the right SFG to the amygdala was associated with a plasma prostaglandin E2 level in PDM. The MVPA based on an altered amygdala EC pattern yielded a total accuracy of 86.84% for classifying the patients with PDM and HC. Conclusion Our study is the first to combine MVPA and EC to explore brain function alteration in PDM. The results could advance understanding of the neural theory of PDM in specifying the pain-free period.

Background The study aimed to investigate how acupuncture modulates brain activities across multiple frequency bands to achieve therapeutic effects in PDM. Methods A total of 47 patients with PDM were randomly assigned to the verum acupuncture group and sham acupuncture group with three menstrual cycles of the acupuncture course. The fMRI scans, visual analog scale (VAS) scores, and other clinical evaluations were assessed at baseline and after three menstrual-cycles treatments. The global functional connectivity density (gFCD) analyses were performed between the pre-and post-acupuncture course of two groups at full-low frequency band, Slow-3 band, Slow-4 band, and Slow-5 band. Results After the acupuncture treatments, the patients with PDM in the verum acupuncture group showed significantly decreased VAS scores (p < 0.05). The frequency-dependent gFCD alternations were found in the verum acupuncture group, altered regions including DLPFC, somatosensory cortex, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), precuneus, hippocampus, and insula. The sham acupuncture modulated regions including angular gyrus, inferior frontal gyrus, and hippocampus. The gFCD alternation in DLPFC at the Slow-5 band was negatively in the patients with PDM following verum acupuncture, and S2 at the Slow-4 band was positively correlated with VAS scores. Conclusion These findings supported that verum acupuncture could effectively modulate frequency-dependent gFCD in PDM by influencing abnormal DLPFC at Slow-5 band and hippocampus at the Slow-3 band. The outcome of this study may shed light on enhancing the potency of acupuncture in clinical practice.

Lack of effective drugs for acute kidney injury (AKI) grades 1–2 is a crucial challenge in clinic. Our previously single-center clinical studies indicated Chuan Huang Fang (CHF) might have nephroprotection in AKI on chronic kidney disease (CKD) (A on C) patients by preventing oxidant damage and inhibiting inflammation. Reduced glutathione (RG) has recently been shown to increase the clinical effectiveness of high-flux hemodialysis among patients with severe AKI. In this multicenter randomized controlled clinical study, we designed a new protocol to assess the efficacy and safety of CHF combining RG in patients with A on C. We also explored therapeutic mechanisms from renal fibrosis biomarkers. 98 participants were randomly and equally divided into the RG and RG + CHF subgroups. The RG and RG + CHF groups received general treatments with RG and a combination of RG and CHF, respectively. The therapy lasted for 2 weeks. In this study, the primary assessment result was a difference in the slope of serum creatinine (Scr) over the course of 2 weeks. The secondary evaluation outcomes were alterations in blood urea nitrogen (BUN), uric acid (UA), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers, renal fibrosis biomarkers (transforming growth factor-β 1 (TGF-β 1), connective tissue growth factor (CTGF)), and traditional Chinese medicine (TCM) symptoms. Furthermore, vital signs and adverse events (AEs) were observed. Both groups had a slower renal function decline after treatment than before treatment. Compared with RG group, more reductions of Scr, BUN, UA, and better improvement of eGFR were observed in RG + CHF group (p < 0.05). Additionally, the levels of urinary AKI biomarkers, renal fibrosis biomarkers, and TCM syndromes were decreased in RG + CHF group versus RG group (p < 0.05). No significant between-group differences were observed of AEs. We thus concluded this novel therapy of CHF combining RG might be a useful method for treating A on C patients.

OBJECTIVE:To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea.METHODS:Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group.RESULTS:In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05).CONCLUSION:The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.

The incidence of cancer in the world has been rising in recent years. Although Western medicine has the ability to treat tumors, some Western cancer treatments cause serious and even irreversible damage to the body. Traditional Chinese medicine (TCM) combines the excellence of Chinese philosophy and the cumulative knowledge of thousands of years of clinical practice. TCM has incomparable advantages in the prevention and treatment of tumors. This review summarizes the epidemiological data of tumors and focuses on the pathogenesis theory of tumors. It demonstrates the advantages and shortcomings of TCM in tumor prevention and treatment. Based on our clinical experience, we put forward an optimization plan of TCM treatments of tumors and a plan for the propagation of TCM culture, which we believe will help TCM become more recognized in international medicine.

Background . Acute kidney injury (AKI) is a global public health challenge resulting in considerable morbidity and mortality. AKI on chronic kidney disease (CKD) (AKI on CKD, A on C) accounts for about a third of total AKI. For severe AKI grade 3, renal replacement therapy (RRT) should be implemented in time. However, the lack of recognized drug treatment method for AKI grades 1–2 is a crucial problem in clinic. Chuan Huang Fang (CHF) is a Chinese herbal formulation developed for the treatment of A on C from the Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies suggested that CHF might effectively protect renal functions of A on C patients. As a widely used antioxidant in clinic, reduced glutathione (RG) is reported to improve the clinical efficacy of high-flux hemodialysis (HFHD) in severe AKI patients recently. To address the crucial problem mentioned above, thus we design a new clinical protocol of CHF combining RG and try to evaluate the efficacy and safety of this protocol in treating patients diagnosed with CKD stages 2–4 complicated with AKI grades 1–2. Methods . This is a multicenter randomized controlled clinical trial. We intend to enroll 162 participants, and these participants will be divided into the RG group, the CHF group, and the RG + CHF group randomly assigning 1 : 1 : 1 principle. The RG group will be general treatments combining RG, the CHF group will be general treatments combining CHF, and the RG + CHF group will be general treatments combining RG and CHF. The duration of treatment will last two weeks. The primary evaluation outcome will be the change in the slope of serum creatinine (Scr) over 2 weeks. Secondary evaluation outcomes include changes in blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), gamma-glutamyl transpeptidase ( γ -GT), etc.), traditional Chinese medicine (TCM) symptoms, inflammatory indicators, and oxidative stress indicators. Meanwhile, the vital sign indicators and adverse events (AEs) will be closely observed. These dates will be meticulously recorded and properly handled by investigators throughout the study. Discussion . This study will provide convictive research-derived data to evaluate clinical efficacy and safety of CHF combing RG for CKD stages 2–4 complicated with AKI grades 1–2 and provide an evidence-based recommendation for clinicians. The timely completion of this trial will provide a novel drug treatment method for A on C. This trial is registered with ChiCTR2100043311 and registered on February 9, 2021.

Acupuncture or moxibustion has been proven to be effective for patients with primary dysmenorrhea (PDM). However, the respective advantages and potential central mechanism of acupuncture and moxibustion are worthy of investigating to promote their further application. In this randomized controlled neuroimaging trial, 72 patients with PDM will be randomly assigned to three groups: acupuncture treatment group, moxibustion treatment group, and waiting list group. The acupuncture treatment group and moxibustion treatment group will receive acupuncture or moxibustion, respectively, for a total of 3 sessions over 3 consecutive menstrual cycles, and the waiting list group will not take acupuncture or moxibustion during these 3 menstrual cycles. The COX Menstrual Symptom Scale (CMSS), visual analog scale (VAS), and Pain Catastrophizing Scale (PCS) will be used to evaluate the clinical efficacy. The Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and 36-Item Short Form Health Survey (SF-36) will be used to assess the mental state and quality of life at baseline and at the end of treatment. Functional magnetic resonance imaging (fMRI) will be performed for detecting the cerebral activity changes at baseline and at the end of the treatment. The clinical data and imaging data will be analyzed among the groups. Correlation analysis will be conducted to investigate the relationship between brain functional changes and symptom improvement. The application of the randomized controlled neuroimaging trial will provide objective and valid evidence about how acupuncture and moxibustion treatment relieve menstrual pain. The results of this study would be useful to confirm the potential similarities and differences between acupuncture and moxibustion in clinical efficacy and central mechanism for patients with PDM. Chinese Clinical Trial Registry ChiCTR2100043732 . Registered on 27 February 2021

Objective: To obtain evidence-based conclusions about the effect of acupuncture on pain relief in women undergoing oocyte retrieval, the results of randomized controlled trials (RCTs) that met the criteria were assessed on the Pain Assessment Scale and pregnancy indicators. Search Methods: References were retrieved in MEDLINE, EMBASE, CNKI database, CBM database, VIP database, and Wanfang database from inception to June 26, 2021. Unpublished ongoing trials were searched in the Clinical Trials Registries. This review included RCTs that investigated the acupuncture analgesic effects during oocyte retrieval in women undergoing in vitro fertilization. Results: Fourteen RCTs (2503 women in total) with six types of comparisons were finally included. The quality of concluding evidence was generally low or very low. Performance bias and outcome assessment bias was the main risk of bias of the included studies. Acupuncture combined with conscious sedation and analgesia (CSA) was associated with less intraoperative (SMD=− 1.03; 95% CI: − 1.71 to − 0.36) and postoperative (SMD = − 1.11; 95% CI: − 1.51 to − 0.71) pain compared to receive CSA alone in oocyte retrieval. Acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) was more effective than using NSAIDs alone for postoperative analgesia (MD = − 1.76; 95% CI: − 2.08 to − 1.44). Conclusion: Acupuncture complex analgesic therapy is more effective than utilizing CSA or NSAIDs alone. Furthermore, there is no significant consensus on whether there is an analgesic effect of applying acupuncture alone during oocyte retrievals, which needs further research. The overall results should be interpreted with caution due to the high risk of bias/low-GRADE scores among these studies. Protocol and Registration: PROSPERO registration number: CRD42020170095. Keywords: acupuncture, analgesia, oocyte retrieval, meta-analysis, systematic review