Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To investigate the effect of signals mediated by activated CD28 in promoting survival of multiple myeloma (MM) cells and metabolic fitness and its possible mechanism. METHODS: The expression of CD28 on 4 MM cell lines (XG2, XG1, RPMI 8226 and U266) was determined by flow cytometry. Two cell lines with the highest or lowest CD28 expression were selected. The proliferation, cell cycle, migration and apoptosis of MM cells in vitro were determined in medium containing high glucose concentration or CD28 agonist monoclonal antibody with different bioassays. shRNA interference assay was used to knock down the expression of CD28 on U266 cells. Then, the effect of activated CD28 on glucose uptake rate and drug resistance in MM cells were analyzed using fluorescent glucose analogues (2-NBDG). The expression of Glut1/4, HkII and Fasn was determined with real time quantitative PCR. RESULTS: Flow cytometry analysis showed that all the four tested MM cell lines expressed CD28 and U266 cells had the highest positive rate. The results of in vitro experiment showed that CD28 activation could significantly up-regulate the expression of Glut4 and HkII, promote MM cell metabolic remodeling, enhance 2-NBDG/glucose uptake, increase energy metabolism, thereby elevating cell proliferation and migration abilities, leading to an increase in the number of cells in S- and G₂-phases. Meanwhile, activated CD28 subsequently up-regulated resistance of MM cells to bortezomib or dexamethasone. CONCLUSION MM cells express high levels of CD28 abnormally, and activation of CD28 can promote up-regulation of glucose uptake in MM cells, thereby promoting cell proliferation and enhancing drug resistance.
Humans ; Multiple Myeloma/pathology* ; CD28 Antigens/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Glucose/metabolism* ; Glucose Transporter Type 4/metabolism* ; Glucose Transporter Type 1

Objective： To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood therapy for the treatment of diabetic mellitus erectile dysfunction. Methods： China National Knowledge Infrastructure(CNKI), Wanfang Data, VIP, Chinese Biomedical Database(CBM), PubMed, Cochrane Library, Embase and Web of Science were searched from inception until October 20th of 2024，for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction. Literature screening, quality evaluation, and data extraction were carried out in accordance with relevant standards. The software of RevMan5.4 was used for the analysis of publication bias. And meta-analysis was conducted to assess the impact of this therapy on IIEF-5, total effective rate, adverse reactions. The evidence levels according to the analysis results were evaluated. Results: Totally 19 RCTs were included, involving 1 612 patients. The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores (MD=3.59，95%CI［2.14，5.03］，P<0.01)，total effective rate (OR=4.30，95%CI［3.29，5.32］，P<0.000 01）. However, there was no statistically significant difference in the incidence of adverse reactions(OR=0.98，95%CI［0.48，2.01］，P=0.96) between the two groups. Conclusions： Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction. But considering the limited quantity of included studies, more high-quality studies still be needed to validate the therapeutic effect.
Humans ; Male ; Erectile Dysfunction/therapy* ; Randomized Controlled Trials as Topic ; Kidney ; Medicine, Chinese Traditional ; Diabetes Complications/therapy*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.