Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Objective To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum.Methods A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template.In 3D-printing group,there were 14 patients,includ-ing 10 males and 4 females;aged from 21 to 53 years old;CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted.In conventional group,there were 15 patients,including 10 males and 5 females;aged from 19 to 55 years old;conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted.Blood loss,surgical time,radiographic quality of reduction,and hip function were compared between groups.Results The difference in operation time and intraoperative blood loss was significant(P＜0.05).Twenty-three patients were followed up from 12 to 30 months,and the fractures in both groups healed with a healing time of 3 to 6 months.At the last follow-up,the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conven-tional group(P＜0.05),with no significant differences in walking ability,hip mobility and total score(P＞0.05).In 3D printing group,6 cases were excellent,5 cases were good,3 cases were fair;in conventional group,5 cases were excellent,5 cases were good,4 cases were fair,1 case was worse;no significant difference between two groups(P＞0.05).Conclusion Virtual preopera-tive planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery,im-prove the quality of reduction.This method is efficient,accurate and reliable to treat acetabular posterior wall fractures.

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.
Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Liver Neoplasms/drug therapy* ; Aconitum ; Ligands ; Mice, Inbred C57BL ; Killer Cells, Natural/metabolism* ; Chemokines/pharmacology* ; Cell Line, Tumor

Objective:To evaluate the dose-response relationship of remimazolam for loss of consciousness during anesthesia induction in the patients undergoing coronary artery bypass grafting (CABG).Methods:American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳpatients, aged 55-64 yr, with body mass index of 21-26 kg/m 2, scheduled for elective CABG under general anesthesia, were included in this study.The trial was conducted using the modified Dixon′s up-and-down method. The initial dose of remimazolam was 0.225 mg/kg, each time the concentration increased/decreased by 0.025 mg/kg in the next patient depending on whether or not the patients lost consciousness. Criteria for loss of consciousness was considered as the modified vigilance sedation score≤1 within 3 min after remimazolam administration. The 50% effective dose (ED 50), 95% effective dose (ED 95) and their 95% confidence interval ( CI) was analyzed by probit probability analysis method. Results:The ED 50 of remimazolam for loss of consciousness during anesthesia induction was 0.175 mg/kg, 95% CI was 0.163-0.185 mg/kg, ED 95 was 0.211 mg/kg, and 95% CI was 0.197-0.255 mg/kg. Conclusions:The ED 50 and ED 95 of remimazolam were 0.175 and 0.211 mg/kg respectively when used for loss of consciousness during anesthesia induction in the patients undergoing CABG.

A user-friendly teaching software for visual analysis of acupoint compatibility laws has been developed based on the principles of partial order mathematics. This software is designed to provide auxiliary teaching of structured organization and visualization of law knowledge of compatibility data of acupuncture and moxibustion prescriptions from ancient texts, textbooks, and clinical case records. The software is installed as a plugin in the Microsoft Office Excel, allowing the generation of visually appealing graphs and associated rules that align with the cognitive patterns of teachers and students majoring in acupuncture and moxibustion. Its aim is to facilitate the discovery and analysis of underlying patterns and structured knowledge embedded in acupoint compatibility data, thus contributing to the enhancement of teaching effectiveness in acupoint compatibility.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Moxibustion ; Acupuncture ; Software ; Meridians

Bibliometric and scientific knowledge graph methods were used to analyze the research status and hot spots of acupuncture-moxibustion in treatment of myofascial pain syndrome (MPS) and explore its development trend. The articles of both Chinese and English versions relevant to MPS treated by acupuncture-moxibustion were searched in CNKI, VIP, Wanfang, SinoMed and WOS from the database inception to March 20, 2023. Using Excel2016, CiteSpace6.2.R2 and VOSviewer1.6.18, the visual analysis was conducted by means of the cooperative network, keyword co-occurrence, keyword timeline, keyword emergence, etc. From Chinese databases and WOS database, 910 Chinese articles and 300 English articles were included, respectively. The annual publication volume showed an overall rising trend. Literature output of English articles was concentrated in Spain, China, and the United States, of which, there was less cross-regional cooperation. In the keyword analysis, regarding acupuncture-moxibustion therapy, Chinese articles focused on "acupuncture", "electroacupuncture" and "acupotomy"; while, "dry needling" and "injection" were dominated for English one. Clinical study was the current hot spot in Chinese databases, in comparison, the randomized controlled double-blind clinical trial was predominant in WOS. Both Chinese and English articles were limited in the report of mechanism research. The cooperation among research teams should be strengthened to conduct comparative research, dose-effect research and effect mechanism research with different methods of acupuncture-moxibustion involved so that the evidences can be provided for deeper exploration.
Humans ; Moxibustion ; Pattern Recognition, Automated ; Acupuncture Therapy ; Myofascial Pain Syndromes/therapy* ; Electroacupuncture

OBJECTIVES: To observe the changes of skin blood flow perfusion at Waiguan (TE 5) caused by mild moxibustion with moxa stick and infrared mild moxibustion using laser speckle contrast imaging technology, and to compare the microcirculatory effect during and after both moxibustion methods and explore the dose-response relationship of moxibustion. METHODS: Twenty-four healthy participants were treated with mild moxibustion with moxa stick and infrared mild moxibustion at left Waiguan (TE 5). The record started when the skin temperature reached (44±1) °C, and both moxibustion methods were provided within this temperature range. The 20-minute moxibustion process was divided into four stages (5, 10, 15, and 20 min) using interpolation method, and each participant completed eight interventions with a minimum 24-hour interval between different interventions. The skin surface temperature of the left Waiguan (TE 5) was monitored when both moxibustion interventions were given for 10 min using a TES1306 thermocouple thermometer. The skin microcirculatory blood perfusion units (MBPU) of left Waiguan (TE 5) was measured using a PSIN-01087 laser speckle blood flow imager 1 min before moxibustion, at 5, 10, 15, 20 min during moxibustion and continuously for 20 min after moxibustion in each intervention. RESULTS: The skin surface temperature of the left Waiguan (TE 5) remained within the range of (44±1) °C during both moxibustion methods, with no statistically significant difference (P>0.05). Compared with that before moxibustion, the MBPU of the left Waiguan (TE 5) was increased significantly at 5, 10, 15, and 20 min of both moxibustion methods (P<0.05, P<0.01). Compared with moxibustion for 10, 15 and 20 min, the MBPU of the left Waiguan (TE 5) of moxibustion for 5 min was lower in both moxibustion methods (P<0.01). For both moxibustion methods with the same moxibustion course, the MBPU of the left Waiguan (TE 5) 20 min after intervention was significantly higher than that at 1 min before moxibustion (P<0.001), and there was no significant difference in MBPU between 1 min before moxibustion and 20 min after moxibustion among different groups (P>0.05). Within the same moxibustion method, the MBPU of the left Waiguan (TE 5) 20 min after moxibustion with the intervention of 5 min was lower compared to that of 10, 15, and 20 min of moxibustion (P<0.001), with no significant differences between 10, 15, and 20 min of moxibustion (P>0.05). CONCLUSIONS When controlling the skin temperature at Waiguan (TE 5) within (44±1) °C, infrared mild moxibustion has similar effects on skin microcirculatory blood perfusion as traditional mild moxibustion with moxa sticks. From a dose-response perspective, microcirculation reached a stable state after 10 min of moxibustion, and moxibustion interventions lasting for more than 10 min shows better therapeutic effects.
Humans ; Moxibustion/methods* ; Microcirculation ; Skin/blood supply* ; Skin Temperature

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Human respiratory syncytial virus (HRSV) is one of the main pathogen causing severe acute lower respiratory tract infections in infants and the elderly, with high incidence rate and mortality worldwide. Vaccine is one of the important measure to prevent infection, transmission and severe disease of HRSV, but currently there is no officially approved preventive vaccine for prevention of HRSV in the world. This paper reviews and analyzes the current research and development progress of HRSV vaccine, summarizes the design routes of different types of HRSV preventive vaccines, and discusses the difficulties and challenges in vaccine research and development, in order to provide reference for the research and development of HRSV vaccine and the development of clinical trials.
Infant ; Humans ; Aged ; Respiratory Syncytial Virus, Human ; Respiratory Syncytial Virus Infections/epidemiology* ; Respiratory Syncytial Virus Vaccines/therapeutic use* ; Respiratory Tract Infections